Background and objectives:The relationship between serum potassium (S K ) and mortality in chronic kidney disease (CKD) has not been systematically investigated.Design, setting, participants, & measurements: We examined the predictors and mortality association of S K in the Renal Research Institute CKD Study cohort, wherein 820 patients with CKD were prospectively followed at four US centers for an average of 2.6 years. Predictors of S K were investigated using linear and repeated measures regression models. Associations between S K and mortality, the outcomes of ESRD, and cardiovascular events in time-dependent Cox models were examined.Results: The mean age was 60.5 years, 80% were white, 90% had hypertension, 36% had diabetes, the average estimated GFR was 25.4 ml/min per 1.73 m 2 , and mean baseline S K was 4.6 mmol/L. Higher S K was associated with male gender, lower estimated GFR and serum bicarbonate, absence of diuretic and calcium channel blocker use, diabetes, and use of angiotensinconverting enzyme inhibitors and/or statins. A U-shaped relationship between S K and mortality was observed, with mortality risk significantly greater at S K <4.0 mmol/L compared with 4.0 to 5.5 mmol/L. Risk for ESRD was elevated at S K <4 mmol/L in S K categorical models. Only the composite of cardiovascular events or death as an outcome was associated with higher S K (>5.5).Conclusions: Although clinical practice usually emphasizes greater attention to elevated S K in the setting of CKD, our results suggest that patients who have CKD and low or even low-normal S K are at higher risk for dying than those with mild to moderate hyperkalemia.