Objective: Previously we observed an attenuation of body temperature in lactating rats treated with lipopolysaccharide (LPS) compared with virgin saline-treated females. We proposed that high levels of prolactin (PRL) during lactation may induce this attenuation because PRL has a suppressive effect on inflammation. In the present study, we induced hyperprolactinemia in female virgin rats to investigate the effects of PRL on body temperature and sickness behavior induced by LPS. Methods: To induce hyperprolactinemia, female rats in the estrous phase received domperidone 3 times/day for 5 days and an LPS injection (D + LPS group). Two other groups were treated with saline solution for 5 days, and one of them received a saline injection (S + S group) and the other LPS (S + LPS group). Tympanic temperature was assessed 0, 2, 4, 6, 8, 10, 24, 48, 72, and 96 h after treatment. Body weight gain and food and water consumption were observed 24, 48, 72, and 96 h after treatment. Results: Hyperprolactinemia impaired LPS-induced hypothermia and hyperthermia phases of body temperature. Body weight gains in the S + LPS group and the D + LPS group were similar. A decrease in food consumption was observed in the D + LPS rats at 72 and 96 h compared to the S + LPS group. Conclusion: Hyperprolactinemia impaired the body temperature increase induced by LPS and several signs of sickness behavior, suggesting that febrile responses to LPS can be modulated by the physiological state. These phenomena may have adaptive value for reproduction.