Introduction: Depression among human immunodeficiency virus (HIV)-seropositive individuals has been associated with reduced quality of life. Objective: To evaluate the effect of depressive symptoms and HIV exposure on mean quality of life scores in HIV-seropositive and HIV-seronegative postpartum women. Methods: A cross-sectional study was conducted with two groups: 80 HIV-seropositive and 80 HIV-seronegative postpartum women. The Edinburgh Postnatal Depression Scale and the World Health Organization Quality of Life short-version scale were used to assess presence of depressive symptoms and quality of life scores. Two-way analysis of variance was used to compare the effects of depressive symptoms, HIV exposure and interaction between depressive symptoms and HIV exposure on mean quality of life scores, with p < 0.05 considered statistically significant. Results: Depressive symptoms were present in 35% (28) of HIV-seropositive and 17.5% (14) of HIV-seronegative participants (p = 0.02). The interaction between depressive symptoms and HIV exposure was not significant for any quality of life domain. The main effect of HIV exposure was also not significant. Depressive symptoms had a negative influence on quality of life scores in all domains (physical health, psychological health, social relationships and environment) (p < 0.001). Conclusion: The quality of life of pregnant women is negatively influenced by the presence of depressive symptoms.  Keywords: Pregnancy; quality of life; depression and HIV