Honey bees (Apis mellifera) are exposed to sublethal doses of insecticides, but little is known about insecticide effects on their survivorship associated to health-related gene expression. To test the effect of sublethal doses of clothianidin, imidacloprid and carbaryl on the lifespan and health of honey bees, workers were orally and topically exposed to LD5 doses of these insecticides. The survivorship of treated bees was monitored and the expression of three immune-related genes, hymenoptaecin (AmHym), basket (AmBask) and lysozyme (AmLyso2) was analyzed at 24 and 72 hours post treatment (hpt), as well as that of the antioxidant-related gene vitellogenin (AmVit2), the poly-U binding factor (AmPuf68), and the detoxification gene cytochrome P450 (AmCYP9Q3). The three insecticides significantly reduced the length of life of bees but the mode of application did not affect survivorship. AmHym, AmBask and AmVit2 expression was significantly down-regulated at 72 hpt in bees treated with clothianidin and imidacloprid, indicating immunosuppression. However, AmLyso2, AmCYP9Q3 and AmPuf68 were significantly up-regulated. The down-regulation of AmVit2 could have caused decreased resistance to oxidative stress. AmPuf68 expression could be associated with increased protection against xenobionts. AmCYP9Q3 was up-regulated at 24 and 72 hpt in oral exposures, but only until 72 hpt in topical exposures, indicating faster sensitivity towards detoxification mechanisms in oral treatments. This study demonstrated detrimental effects of sublethal doses of clothianidin, imidacloprid and carbaryl on honey bee survivorship, immunity and antioxidant mechanisms, and an induction of defense and detoxification responses that could be physiologically costly to the bees.