Prepartum and postpartum depression have negative, and sometimes devastating, effects on women and their families. As inflammatory processes are related to depression in general, we hypothesized that inflammatory perturbations, prepartum and postpartum, contribute to triggering and worsening of symptoms of peripartum depression. We conducted a longitudinal preliminary study on 27 women at high risk for developing postpartum depression measuring SIGH-SAD scores at three time points: 35-38 weeks gestation, 1-5 days postpartum, and 5-6 weeks postpartum. Serum C-reactive protein and interleukin-6, both markers of inflammation, as well as tryptophan, kynurenine, and the kynurenine/tryptophan ratio, as consequences of inflammation and pathophysiological steps towards depression, were measured at each time point. C-reactive protein levels were found to be positively related to atypical and total depression scores in the prepartum period and with atypical depression scores in the early postpartum period. Tryptophan was found to be negatively associated with total depression scores in the prepartum, as well. These findings warrant further investigation that could lead to novel interventions to decrease poor outcomes from peripartum depression.