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In mice a 50% calorie restriction (CR) for 28 days attenuates sickness behavior after lipopolysaccharide (LPS) and these mice demonstrate a central anti-inflammatory bias. This study examined the dose-dependent effect of CR on sickness behavior (fever, anorexia, cachexia) and peripheral immune markers post-LPS. Male Sprague–Dawley rats fed ad libitum or CR by 50% for 14, 21, or 28 days were injected on day 15, 22, or 29 with 50 μg/kg of LPS or saline (1 mL/500 g). Changes in body temperature (T_b), locomotor activity, body weight, and food intake were determined. A separate cohort of rats was fed ad libitum or CR by 50% for 28 days and serum levels of corticosterone (CORT), interleukin 6 (IL-6), and IL-10 were determined at 0, 2, and 4 h post-LPS. The rats CR for 28 days demonstrated the largest attenuation of sickness behavior: no fever, limited reduction in locomotor activity, no anorexia, and reduced …