Postpartum depression (PPD) is a devastating disorder that may carry lifetime consequences. Although several psychosocial risks for PPD have been identified, biological contributors are unclear. Elevated inflammatory cytokines contribute to depression in nonpregnant, nonpostpartum populations; yet, their role in PPD has been minimally studied. The objective of this study is to determine whether inflammatory cytokines early in the postpartum period contribute to the development of PPD. Women were recruited within 24 hr of delivery, and 26 provided urine for analysis of interleukin-1 beta (IL-1beta) and interleukin-6 (IL-6) on postpartum days 7, 14, and 28. Participants completed a depression symptom survey (Centers for Epidemiologic Studies Depression Scale; CES-D) on Day 28. An increase in IL-1beta was seen on Day 14 in women with symptoms of depression (CES-D > or = 11) on Day 28 compared to levels in women without depressive symptoms (F = 4.50, p = .045). These preliminary findings suggest elevated IL-1beta early in the postpartum period may increase the risk of PPD. Further studies involving a larger sample of women, including those clinically diagnosed with PPD, are required.