Background: Cervical cancer patients experience serious quality of life (QOL) disruptions, which may include persistent emotional distress. Predictors of persistent or significant depression and anxiety are examined in this study. Methods: A randomized trial tested the efficacy of a psychosocial telephone counseling intervention designed to improve QOL and decrease emotional distress.The FACT-Cx Trial Outcome Index (FACT-Cx-TOI), depression and anxiety (PROMIS short forms) were collected at baseline (T1), 4 months (T2) and 9 months (T3) post enrollment. Multivariate linear and logistic regression models were used to identify predictors of distress at follow-up. Tested predictors included demographic information, stage, treatment assignment, and baseline FACT-Cx TOI and PROMIS scores. Results: 115 women were randomized to PTC and 89 to usual care, with 82% compliance for T2 and 75% at T3. PTC patients experienced a significantly greater reduction in depression from T1 to T2 compared to UC (p=0.014). At baseline, 45% of participants reported depression T-scores above 55 (0.5 SD above the US general population average), and 26% reported levels greater than 60 (>1 SD worse than average). PTC patients were significantly less likely to have depression scores >55 at T2, and significantly more likely to improve by ≥5 points at T2 after adjusting for baseline and disease characteristics. Participation in PTC, higher baseline depression and higher baseline TOI were significant independent predictors of improvement in depression from T1 to T2. Conclusions: Early identification of patients with poor QOL and significant depression can inform supportive care interventions, with potential to improve health outcomes. Funding Source: NCI R01 CA118136-01. Clinical trial information: NCT00496106.