To investigate the role of infection and noninfectious inflammation in epidural analgesia-related fever. This was an observational analysis of placental cultures and serum admission and postpartum cytokine levels obtained from 200 women at low risk recruited during the prenatal period. Women receiving labor epidural analgesia had fever develop more frequently (22.7% compared with 6% no epidural; P=.009) but were not more likely to have placental infection (4.7% epidural, 4.0% no epidural; P>.99). Infection was similar regardless of maternal fever (5.4% febrile, 4.3% afebrile; P=.7). Median admission interleukin (IL)-6 levels did not differ according to later epidural (3.2 pg/mL compared with 1.6 pg/mL no epidural; P=.2), but admission IL-6 levels greater than 11 pg/mL were associated with an increase in fever among epidural users (36.4% compared with 15.7% for 11 pg/mL or less; P=.008). At delivery, both febrile and afebrile women receiving epidural had higher IL-6 levels than women not receiving analgesia. Epidural-related fever is rarely attributable to infection but is associated with an inflammatory state.