一具感染了致命病毒的尸体被扔在了洛杉矶卫生中心外面。Tony和Michelle结了婚，并且已是CTU的主管。他接到了来自一个名为Hector Salazar的墨西哥毒枭的恐吓，他声称如果不把他的哥哥Ramon释放，会有更多的人感染上这种病毒。事实上，Ramon是Jack通过做卧底抓回来的。就在Jack和他的新搭档Chase审问Ramon时，Ramon杀死了自己的律师，并且对Jack他们说了一些奇怪的话。Palmer总统还活着，并且三年来首回洛杉矶，目的是参加新一轮总统竞选的辩论会。他的弟弟Wayne成了他的首席助手，而他的私人医生Anne Packar成了他的女友。一个名叫Kyle Singer的年轻人拿着一包看似毒品的白色粉末，他晚些时候要把这包东西送到交易人的手里，而同时Salazar的手下正在监视Kyle。Kim此时也在CTU工作，并且和Chase交往了三个月。Kim决定在今天把这件事告诉Jack，但是Jack似乎染上了毒瘾

Jack and Chase quarrel over Chase's relationship with Kim. Meanwhile, they learn of a lead to the possible whereabouts of the virus after rading a crackhouse. Linda breaks up with Kyle when she learns that he is planning to make a drug delivery. Wayne approaches Palmer with information about his girlfriend that could damage his chances for reelection, while a CTU employee is not what he seems.

在Tony受伤之后，Michelle忍着伤痛接手Tony的工作。Kyle和Linda最终被Hector的手下关押起来。Jack秘密联系 Palmer总统，请求允许他劫狱来拯救百万人的生命，Palmer总统默许。由于Chase的插手，Jack的劫狱计划遭到了意外。在Anne的劝阻下，Palmer总统拒绝向Anne前夫的勒索妥协。

Jack's efforts to break Ramon out of prison go awry when they are captured by a group of inmates during the riot. Chloe unwittingly stumbles on to Jack's drug problem and she is forced to reveal his secret to Kim and Michelle. Palmer begins his debate with Keeler, while Kyle prepares to sacrifice himself to save Linda.

Jack and Ramon struggle to evade the authorities, while Palmer must shut the debate down because of the prison break. Kim accidentally stumbles on to Gael's secret communications, but she isn't able to warn Michelle in time. The Singer family learns a startling piece of news about Kyle's health.

在飞往墨西哥的飞机上，Ramon把Jack监禁了起来。在Ramon想杀死Jack的紧要关头，Jack成功地逆转局面，反而把Ramon扣为了人质。在飞机抵达墨西哥后，Ramon才得知一开始Jack和Hector就达成了协议，设法把Ramon从监狱中弄出来。Gael被CTU逮捕。正当 Chappelle审问Gael的时候，Tony从医院回来，宣布他和Gael以及Jack在进行一项秘密的病毒拦截活动，而Gael和Jack所做的一切都是这个计划中的一部分。Anne接到前夫的电话，要她去他那儿取她无罪的证据。与此同时，Chase独自一人正前往墨西哥营救Jack。

Palmer and Chappelle view a message from Jack, explaining his undercover work with the Salazars. Meanwhile, Hector tries to convince Ramon that they should deal with Bauer so that they can get their hands on the virus. Jack has a private moment with Claudia and she blasts him for leaving her behind when he arrested Ramon. Chase arrives in Mexico, but is captured by Hector's men. Ramon devises a way for Jack to prove his loyalty to them. Anne manages to clear Palmer's name, but she breaks off her relationship with him.

Palmer clears Anne's name with the press, but he finds that he is facing a new problem when his biggest campaign contributer reveals a startling secret about Wayne. Kim and Michelle worry about Tony's mental ability when he continues to make mistakes. Jack and the Salazars meet with Amador, but the deal turns sour when Nina Myers appears on the scene and competes for the virus.

Claudia manages to free Chase from his captors, but she pays a high price for her efforts. Wayne turns to Julia, while Palmer calls on Sherry for help against Milliken. Jack and Ramon make plans to get to Nina, in the hopes of intercepting the virus. Chloe's work at CTU is disrupted when she is forced to take care of her baby.

Jack forces Nina to work with him in order to get the virus from Amador. Palmer meets with Sherry and convinces her to help him deal with Milliken. Chase remains in Mexico to help with the capture of the virus. Ramon and Hector quarrel when Hector wants to pull out of the deal.

在病毒交易地点，一场混战开始了。最终Amador顺利逃脱。而Ramon得到的病毒被证明是定时炸弹，而他也被炸死。Nina逃过了本是为她设计的炸弹，但被Jack和Chase逮住。Kim发现Chloe的婴儿不是她的，准备向上级汇报。而Sherry找到了一个对Alan Milliken不利的证人，但是那位证人转眼就神秘地失踪了，只留下了一滩血迹。

Jack and Chase interrogate Nina, but the worm turns when she causes havoc with the CTU computer systems. Chappelle puts Chloe under guard when she refuses to answer questions about the baby, but is forced to release her when she is the only one who can deal with the crisis. Sherry takes her battle directly to Alan, forcing Julia to act as her accomplice.

在Tony的质问下，Nina终于说出了Alvers这个名字。Chappelle强迫Jack去做一个身体检查，原因是CTU发现了Jack的毒瘾。 Chloe的婴儿其实是Chase和前女友生的。Kim得知这个消息后十分吃惊。Palmer总统在得知Alan Milliken的死讯后质问Sherry是否与此事有关，Sherry否认。Julia秘密地打电话给Wayne，告诉了他事实的真相。

Chappelle threatens to pull Jack from the investigation for killing a material witness, but Jack persuades him to hold off when they find a fresh lead on Amador's whereabouts. Amador and Alvers meet with the man who is planning to unleash the virus in LA within the hour. Michelle and Gael locate the target area, but things really hit the fan when they attempt to capture Alvers in the process of releasing the virus. Wayne argues with Sherry over the consequences of Milliken's death as the police turn up the heat on Julia.

Jack and Chase track Amador in the hopes that he can lead them to the man behind the virus attack. Michelle faces a mob riot when the hotel is quarantined. Sherry extorts Palmer, forcing him to manufacture her alibi for the police.

Saunders begins making demands on the President. He forces Palmer to hold a strange press conference and then orders the death of the CTU agent who can trace him. Jack learns of a woman who can lead him to Saunders, but a surprise attack shifts the balance of power. As Gael's symptoms get worse, Michelle devises a way to relieve the suffering of the victims at the hotel.

Jack and Chase race against time to capture Saunders before the deadline, while Chappelle plans an escape. Michelle begins a frantic search when she learns that an infected hotel guest may have slipped through her fingers.

Jack reluctantly works with Kim on an under-cover job that may help them gain an advantage over Saunders. Palmer informs his cabinet of the crisis, while Saunders makes yet another demand. Chase tracks down the man who left the hotel and learns that the virus is spreading to the general public.

Jack attempts to use Saunders' daughter as leverage to gain control of the virus, while Palmer must deal with the discontented press. Michelle gets the results of her test, while Adam finds that the virus has struck too close to home. Tony finds himself compromised when Saunders exploits his only weakness.

Tony works to free Jane from CTU before Saunders can harm Michelle, but Chloe and Jack become suspicious of his activities. Sherry meets with Palmer's political rival and proposes a deal to blackmail him.

Jack and Tony clash as the time for the hostage exchange draws near. Keeler meets with Palmer and demands his resignation, while Wayne begins a secret operation against Sherry.

Jack pushes the envelope in an attempt to force Saunders to disclose the location of the missing vials. Sherry meets with David to discuss her terms, while Wayne breaks into her home to find the incriminating evidence. Tony finds himself facing a harsh penalty because of his efforts to save Michelle.

Jack and Chase must make a powerful sacrifice when dealing with the virus. Tony is able to help Jack one last time before he is taken into custody, while an angry victim seeks vengeance on Saunders. Palmer makes a surprising career choice in the wake of Sherry's death.