OBJECTIVE Normal pregnancy has been proposed to be a state of physiologic activation of the innate limb of the immune response. Recent studies have concluded that normal pregnancy produces inflammatory changes in peripheral blood leukocytes akin to those of sepsis. This unexpected observation has implications that are critical to understanding the susceptibility of pregnant women to sepsis, the pathophysiology of preeclampsia, and the biology of normal pregnancy. This study was designed to examine the phenotypic and metabolic characteristics of monocytes and granulocytes in normal pregnancy and in pregnant patients with acute infection. METHODS A cross-sectional study was conducted that included nonpregnant women (n = 20), normal pregnant women (n = 57), and pregnant women with a positive blood culture and/or pyelonephritis (n = 16). Phenotypic and metabolic characteristics of monocytes and granulocytes were studied with the use of flow cytometry and monoclonal antibodies against surface markers (CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR). Intracellular reactive oxygen species were measured at basal conditions and after stimulation (oxidative burst). The stimulation index (ratio of intracellular reactive oxygen species after oxidative burst over basal state) was calculated. Nonparametric statistics were used. A probability value of <.01 was considered statistically significant. RESULTS Granulocytes from normal pregnant women had a higher median mean channel brightness for CD14 and CD64, but lower median mean channel brightness for CD16 and HLA-DR than granulocytes of nonpregnant women. Granulocytes of patients with acute infection had a higher median mean channel brightness for CD64 and CD66b than granulocytes of normal pregnant women. Monocytes from patients with acute infection had a higher mean channel brightness for CD11b, CD16, CD18, CD49d, CD64, and CD66b than monocytes of normal pregnant women. Baseline intracellular reactive oxygen species, oxidative burst, and stimulation index values were significantly higher in the granulocytes and monocytes of normal pregnant women than in the granulocytes and monocytes of nonpregnant women. Similarly, baseline intracellular reactive oxygen species, oxidative burst, and stimulation index values were higher in women with acute infections than in normal pregnant women. CONCLUSIONS Normal pregnancy was associated with phenotypic and metabolic changes of granulocytes and monocytes; pregnant women with acute infection had more marked phenotypic and metabolic changes of leukocytes than normal pregnant women. These qualitative differences indicate that the innate limb of the immune response is not maximally activated during normal pregnancy.