Background: For patients with CKD, evidence on the optimal dose of physical activity and possible harm with excessive exercise is limited. This study aimed to analyze the dose-response association between leisure-time physical activity (LTPA) and mortality in those with CKD and explore the optimal dose or possible harm associated with increased levels of LTPA. Methods: 4,604 participants with CKD from the 1999 to 2012 National Health and Nutrition Examination Surveys with linked mortality data obtained through 2015 were classified into 6 groups: 0, 1-149, 150-299, 300-599, 600-899, and >= 900 min/week based on the total duration of the self-reported LTPA. Multivariable-adjusted Cox proportional hazards models were used to examine dose-response associations between LTPA and mortality. Results: During the median follow-up of 114 months, 1,449 (31%) all-cause deaths were recorded. Compared to the inactive group (0 min/week), we observed a 22% lower risk of all-cause mortality (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.63-0.97) among participants who performed 1-149 min per week for LTPA. The corresponding HRs and 95% CIs for all-cause mortality for 150-299 and 300-599 min/week of LTPA were 0.79 (0.64-0.97) and 0.74 (0.56-0.98). The benefit appeared to reach a threshold of a 43% (HR, 0.57; 95% CI, 0.36-0.91) lower risk of all-cause mortality among individuals performing 600-899 min/week for LTPA. Importantly, for >= 900 min/week of LTPA, the continued benefits were observed (HR, 0.62; 95% CI, 0.44-0.87). Conclusion: LTPA was associated with lower mortality in those with CKD. The optimal dose was observed at the LTPA level of approximately 600-899 min/week, and there were still benefits rather than the excess risk with LTPA levels as high as >= 900 min/week. Therefore, clinicians should encourage inactive CKD patients to perform LTPA and do not need to discourage CKD patients who already adhere to long-term physical activity.