BackgroundFew modifiable risk factors for epithelial ovarian cancer have been identified. We and other investigators have found that individual psychosocial factors related to distress are associated with higher risk of ovarian cancer. The present study examined whether co‐occurring distress‐related factors are associated with ovarian cancer risk.MethodsFive distress‐related factors were measured repeatedly over 21 years of follow‐up: depression, anxiety, social isolation, widowhood, and, in a subset or women, posttraumatic stress disorder (PTSD). Cox proportional hazards models estimate relative risks (RR) and 95% confidence intervals (CI) of ovarian cancer for a time‐updated count of distress‐related factors, in age‐adjusted models, then further adjusted for ovarian cancer risk factors and behavior‐related health risk factors.ResultsAcross 1,193,927 person‐years of follow‐up, 526 incident ovarian cancers occurred. Women with ≥3 versus no distress‐related psychosocial factors demonstrated increased ovarian cancer risk (HRage‐adjusted = 1.71; 95% CI = 1.16, 2.52). No significant difference in ovarian cancer risk was observed in women with one or two versus no distress‐related psychosocial factors. In the subsample with PTSD assessed, ≥3 versus no distress‐related psychosocial factors was associated with twofold greater ovarian cancer risk (HRage‐adjusted = 2.08, 95% CI = 1.01, 4.29). Further analysis suggested that women at highest ovarian cancer risk had PTSD co‐occurring with any other distress‐related factor (HR = 2.19, 95% CI = 1.20, 4.01). Adjusting for cancer risk factors and health behaviors minimally impacted risk estimates.ConclusionsPresence of multiple indicators of distress was associated with risk of ovarian cancer. When including PTSD as an indicator of distress, the association was strengthened.