Intraperitoneal injection of lipopolysaccharide (LPS) is a common method to induce systemic inflammation, but there is wide variability in the doses given and no standardized measure of inflammatory level. We characterized the inflammatory response in adult male and female C57BL/6 mice following 3 LPS exposure protocols by measuring body weight changes, spleen weight and immune cell composition in the blood using flow cytometry. Mice were injected twice a week for 1 month with either a 200 μL dose of saline or a low dose of LPS (7.5 x 10^4 EU/kg). Half the animals in each condition were injected with a high dose of LPS (7.5 X 10^5 EU/kg) the day before sacrifice. Acute exposure to a high dose of LPS caused a 10.6% decrease in body weight overnight and no significant change in spleen weight. White blood cell and lymphocyte counts decreased and toll-like receptor 4 (TLR4) positive macrophage count increased for both males and females. Exposure to 1 month of low LPS caused no change in the immune cell composition in the blood and body weight, but spleen weights were significantly increased compared to saline animals. 1 month of low LPS followed by high LPS caused an even greater increase in spleen weight than the 1 month low LPS condition, but no other changes. In summary, all 3 LPS exposure protocols led to evidence of an immune response in both sexes, but body weight and blood immune cell composition normalized following chronic low LPS exposure.