《加菲猫的幸福生活 第五季》，讲述一段不平凡的“猫鼠大战”。乔恩坚信只要有加菲猫在，就可以保证家里没有老鼠，但实际上情况并非如此，表面平静的家其实人员众多，热闹非凡…… 老鼠小吱要出走几天，所以他让这个不太聪明的小弟—阿文看管家里。结果小吱离开不久，惹是生非的表哥鼠仔就出现了。

懒惰却又聪明的肥猫、又笨又可爱的傻狗和一个整天迷迷糊糊的主人乔恩之间的搞笑日常故事。

In honor to celebrate the 15th anniversary of Garfield, CBS aired the sixth season in 1993. For this season, the titles changed at the beginning. Instead of showing clips from only the first two seasons, which is what happened for the last three seasons, the titles included more clips from the fifth season, plus some from this season and one from a second season episode "Health Feud", but still retaining a large amount of the original clips. However, the theme tune remained the same. Episodes 90–96 are available on the Garfield and Friends: Volume 4 DVD set. Episodes 97–105 are available on Garfield and Friends: Volume 5 DVD set.

In this season, the show went back to airing one new episode a week, but stayed in the hour-length format, filling up the second half-hour with episodes from previous seasons and some of the prime-time specials from the 1980s. This entire season, along with the second half of season 6, is available on Garfield and Friends: Volume 5 DVD set. Also worth noting is that here, a new theme song was added that was written by J.R. Johnston and Neil Panton. The theme was sung by J.R. Johnston. This theme song was not shown internationally, and as a result, it does not appear on the DVDs (although Garfield's quotations are kept intact). This new introduction sequence used most clips from Seasons 5-7 and a few from the first two seasons, as well as Garfield in Paradise and Garfield's Feline Fantasies. The episodes stopped using a few seconds of the theme playing in the episode title cards after season seven's fourth episode; music from the episodes were used in the title cards until the show ended, even though season six used music from some of their episodes.

1984年，奥登夫妇的六岁儿子罗伦佐患上罕见的ALD(肾上腺白质退化)症，这是医生宣布为无药可治的绝症。但奥登夫妇均不肯放弃希望，以各种方法挑战医学界的不足，并发明了一种特殊配方的油给罗伦佐食用，终于从死亡边缘把他给救了回来，并且造福了其它同患此病症的患病家属。

著名侦探查理·梅欧突然间失去了特有的敏感度，而他精心策划的一次侦破也以失败告终，这使他对自己彻底丧失了自信，请求上级准许退休，现在他还需要完成最后一次秘密行动。查理已经处在了精神崩溃的边缘，内心甚至充满了对杀人不眨眼的黑手党头头奈斯特拉的惧怕。查理向心理医生寻求帮助。幸运的是，他得到了医疗小组的热情帮助，特别是护士朱蒂对他更是关心备至……