Background Interpersonal functioning is a key determinant of psychological well-being, and interpersonal problems (IPs) are common among individuals with psychiatric disorders. However, IPs are rarely formally assessed in clinical practice or within cognitive behavior therapy research trials as predictors of treatment attrition and outcome. The main aim of this study was to investigate the relationship between IPs, depressogenic cognitions, and treatment outcome in a large clinical sample receiving cognitive behavioral group therapy (CBGT) for depression in a community clinic. Methods Patients (N=144) referred for treatment completed measures of IPs, negative cognitions, depression symptoms, and quality of life (QoL) before and at the completion of a 12-week manualized CBGT protocol. Results Two IPs at pre-treatment, 'finding it hard to be supportive of others' and 'not being open about problems,' were associated with higher attrition. Pre-treatment IPs also predicted higher post-treatment depression symptoms (but not QoL) after controlling for pre-treatment symptoms, negative cognitions, demographics, and comorbidity. In particular, 'difficulty being assertive' and a 'tendency to subjugate one's needs' were associated with higher post-treatment depression symptoms. Changes in IPs did not predict post-treatment depression symptoms or QoL when controlling for changes in negative cognitions, pre-treatment symptoms, demographics, and comorbidity. In contrast, changes in negative cognitions predicted both post-treatment depression and QoL, even after controlling for changes in IPs and the other covariates. Limitations Correlational design, potential attrition bias, generalizability to other disorders and treatments needs to be evaluated. Conclusions Pre-treatment IPs may increase risk of dropout and predict poorer outcomes, but changes in negative cognitions during treatment were most strongly associated with improvement in symptoms and QoL during CBGT. © 2013 Elsevier B.V.