Background/Aims: Chronic kidney disease (CKD) and serious mental illness (SMI) are both associated with an increased risk for repeated hospitalization. The objective of this study was to determine if co-occurring SMI exacerbates the risk for subsequent hospitalization, particularly through the emergency department (ED), among people with CKD. Methods: People hospitalized in Washington State from April 2006 to December 2008 were separated into cohorts with diagnoses of CKD (n = 31,166), SMI (defined by schizophrenia and/or mood disorder; n = 20,167) or CKD with co-occurring SMI (n = 717), and a reference cohort without either diagnosis (n = 548,532). Main outcomes were rehospitalization for condition(s) other than mental illness: (1) through the ED; (2) any admission, and (3) admission resulting in death. Cox regression was used to analyze time to main outcomes controlling for prespecified covariates associated with rehospitalization. Results: The risk of rehospitalization via the ED was increased for people with CKD (hazard ratio, HR = 1.24, 95% confidence interval, CI = 1.21-1.28, p < 0.001) and co-occurring SMI (HR = 1.33, 95% CI = 1.29-1.38, p < 0.001) cohorts, but was significantly greater in the combined cohort (HR = 1.55, 95% CI = 1.40-1.73, p < 0.001). Similarly, the risk of any rehospitalization was increased for CKD (HR = 1.21, 95% CI = 1.17-1.25, p < 0.001) and co-occurring SMI (HR = 1.14, 95% CI = 1.11-1.17, p < 0.001) cohorts, while a significantly greater risk was observed for the combined cohort (HR = 1.36, 95% CI = 1.24-1.48, p < 0.001). The risk of rehospitalization resulting in death was not significantly increased in the combined cohort. Conclusion: In people with CKD, co-occurring SMI increased the risk of experiencing rehospitalization, particularly through the ED. Studies of strategies to address SMI in the CKD population are needed to mitigate the risk of repeat hospital admissions.