In monkeys infected with simian immunodeficiency virus (SIV), changes in body temperature and locomotor activity occur after the acute retroviral syndrome stage of the disease. However, alterations to the circadian rhythm of these factors in SIV-infected monkeys have not been reported. To determine whether the circadian rhythm of body temperature and locomotor activity are disrupted during SIV infection, we analyzed the temperature and activity patterns of SIV-infected monkeys through different stages of the disease, progressing to SIV encephalitis by using the cosinor model for circadian oscillation. We found that SIV infection resulted in significant impairments of the amplitude and mean of the circadian rhythm of body temperature and activity and in the acrophase of the circadian rhythm for temperature. These alterations were not related to changes observed in the acute febrile response induced after viral inoculation. In animals killed once marked circadian anomalies were evident, microglia infiltration and macrophage accumulation in the hypothalamus were observed. Together, these results clearly demonstrate that SIV infection compromises aspects of circadian regulation in monkeys, with important implications for physiological functions, including cognition, in HIV-infected individuals.