OBJECTIVES: Rates of perinatal depression and pregnancy hyperglycemia are higher in Hispanic women as compared to non-Hispanic white women. In turn, depressive symptoms may reduce a woman's ability to engage in lifestyle changes that could reduce their subsequent diabetes risk. METHODS: We conducted a secondary analysis using data from Estudio Parto to evaluate sociodemographic, behavioral, psychosocial, and medical factors associated with perinatal depressive symptoms. Estudio Parto was a randomized controlled trial conducted in Western Massachusetts from 2013 to 17. Eligible participants had pregnancy hyperglycemia. The Edinburgh Postnatal Depression Scale (EPDS) was administered at 24-28 weeks gestation and at 6 weeks, 6 months, and 12 months postpartum. An EPDS cutpoint of 10 or greater defined the presence of depressive symptoms. RESULTS: In this sample of Puerto Rican women with pregnancy hyperglycemia, 32% and 27% showed prenatal and postpartum depressive symptoms, respectively. Among participants, 35.5% were diagnosed with GDM, 44.3% with isolated hyperglycemia, and 20.2% with impaired glucose tolerance. In multivariable models, being unmarried (OR 3.87; 95% CI 1.51-9.94), prenatal substance use (smoking or alcohol consumption; OR 2.96; 95% CI 1.41-6.18), and maternal age (1.11 for each year; 95% CI 1.04-1.18) were associated with higher odds of prenatal depressive symptoms. None of the risk factors were associated with subsequent postpartum depression in adjusted analyses. CONCLUSIONS: Identifying factors associated with prenatal and postpartum depression in Puerto Rican women with pregnancy hyperglycemia can inform targeted lifestyle interventions in this at-risk group, increase the likely adoption of healthy lifestyle behaviors, and thereby work to address health disparities. CLINICALTRIALS: gov NCT01679210; date of registration 08/07/2012.