Previous work has shown that psychosocial stress is related to increases in serum levels of pro-inflammatory cytokines late in pregnancy, and a growing body of research suggests that increased inflammatory activity during pregnancy, generally, may have a negative impact on outcome. The present study further addressed these issues by assessing relationships between psychosocial stress, social support and serum cytokines in early, mid, and late pregnancy, and the effects of stress and social support on the production of cytokines by stimulated lymphocytes in late pregnancy. In addition, we examined relationships between stress, support, and serum C-reactive protein (CRP) during pregnancy. Elevated stress was not only related to higher serum IL-6 late in pregnancy as in our prior work, but this relationship was also evident during early pregnancy and elevated stress was also associated with lower IL-10 in early pregnancy. No relationships between stress and cytokines were apparent during the 2nd trimester of pregnancy. Elevated stress during the 2nd trimesters and low social support during the 3rd trimester were related to increased serum levels of CRP, further suggesting that psychosocial factors can contribute increased inflammation during pregnancy. Importantly, elevated stress levels across pregnancy were predictive of elevated production of the pro-inflammatory cytokines IL-1B and IL-6 by stimulated lymphocytes in the 3rd trimester, suggesting that stress during pregnancy affects the function of immune system cells. These findings further support the notion that prenatal stress alters maternal physiology and immune function in a manner consistent with increased risk of pregnancy complications such as preeclampsia and premature labor.