Background: The effect of mild chronic kidney disease (CKD) on depression, stress, quality of life (QOL), and health status is not well understood. We compared these outcomes in subjects with and without CKD. Methods: We performed a cross-sectional study of 967 outpatients enrolled in the Heart and Soul Study. CKD was defined as a measured creatinine clearance <60 ml/min. Outcome measures included depressive symptoms measured using the Patient Health Questionnaire (PHQ), stress measured using the Perceived Stress Scale (PSS), and QOL and overall health rated as excellent, very good, good, fair, or poor. Results: The prevalence of depressive symptoms (17 vs. 19%, p = 0.4) or perceived stress (11 vs. 16%, p = 0.09) did not vary significantly by CKD. The prevalence of fair or poor QOL was not significantly different in subjects with CKD, compared with those without CKD (24 vs. 23%, p = 0.65). Age-adjusted analyses revealed a significant association of CKD with QOL (p = 0.003), however, this association no longer reached statistical significance after adjustment for confounders (p = 0.06). Subjects with CKD were more likely to report poor or fair overall health than subjects without CKD (42 vs. 34%, p = 0.03). After multivariate adjustment, CKD remained significantly associated with worse overall health (OR = 1.65, 95% CI 1.21–2.24, p = 0.001), and modestly associated with QOL (OR = 1.31, 95% CI 0.99–1.75, p = 0.06), but had no association with depression (p = 0.48) or stress (p = 0.24). Conclusion: In this study of persons with coronary artery disease, subjects with CKD had reduced overall health and modestly reduced QOL; however, mental health was similar in those with and without CKD. These findings suggest that self- assessed overall health may decline at earlier stages of renal dysfunction than mental health outcomes or QOL.