Circadian rhythms modulate the bodies immunes system. This study was designed to compare the effect of two circadian rhythm disruptors (daylight-restriction and sleep deprivation) on the immune response of male Swiss mice. Animals where divided into group 1(control; n=10), which were neither daylight-restricted or sleep-deprived and groups 2,3,4 and 5 (n=20/group) respectively. Ten animals each from groups 2-5 were restricted from daylight for 12,24,42 and 72hours respectively while the remaining 10animals per group were sleep-deprived for same time interval. Post-exposure, blood samples were collected into EDTA-lined sample bottles (n=5/subgroup) for haematological indices (eosinophils, neutrophils, platelet, white blood cell (WBC), monocyte, lymphocyte) and plain sample bottles (n=5/subgroup) for serum biochemical assays (interferon-γ, superoxide dismutase (SOD) reduced glutathione (GSH), and malonaldehyde (MDA). Data were analysed with ANOVA at p<0.05. Compared to control, lymphocytes increased (p<0.05) while WBC, platelet and neutrophil reduced from 12-72 hours following either sleep-deprivation or daylight-restriction. Eosinophil’s also increased in the experimental groups from 24-72 hours post-exposure respectively. Daylight restriction increased monocytes 48-72hours while sleep-deprivation increased monocytes at 12,24 and 72hours respectively compared to control. Daylight-restriction increased interferon-γ(pg/ml) at 12(751.8±31.8), 24(745.4±33.8), 48(890.0±30.9) and 72(773.4±53.3) hours while sleep-deprivation at 48(1078±119.1) and 72(909±94.0) hours increased respectively post-exposure compared to control (452.3±43.6). SOD (U/mg protein) in the sleep-deprived group increased at 12(2.86±0.07), 24(2.74±0.08) and 48(4.92±0.13) hours but decreased at 72hours (1.26±0.08) respectively while values in the daylight-restricted animals from 12-72hours (1.38±0.38;0.82±0.17;0.74±0.17;0.82±0.15) decreased (p<0.05) compared to control (2.12±0.31). Compared to controls (28.89±3.47), GSH (mg/ml) in the sleep-deprived group at 12-72hours (22.25±1.31;18.56±4.05;14.86±3.27;9.69±1.15) reduced (p<0.05) while values in the daylight-restricted group increased at 12(44.94±4.59) and 24(33.44±4.49) hours but reduced at 48(17.84±2.04) and 72(13.68±1.97) hours respectively. MDA (mmol/mg protein) at 12-72hours in both sleep-deprived (3.07±0.44;3.65±1.31;2.68±0.18;2.76±0.34) and daylight-restricted (2.73±0.82;3.63±0.99;3.67±0.97;3.14±0.78) groups were increased respectively compared to control(1.77±0.22). This study suggests that the immune system response to daylight restriction maybe faster than that of sleep deprivation. It also suggests that daylight restriction and sleep deprivation may compromise body defense mechanisms and thus predispose to infections and diseases.