Objective There is an urgent need to identify clinical markers that can help physicians determine when additional treatment is necessary to manage the symptoms of knee osteoarthritis (OA). Patterns of physical activity that occur within a day, e.g., low activity in the morning and/or evening, may be a novel means to identify treatment need, given that symptoms may reduce daily activity at specific times of the day. The purpose of this study is to explore the relationship between within‐day patterns of physical activity and all‐cause mortality in adults with or at high risk for knee OA. Methods We performed a secondary analysis of the Osteoarthritis Initiative (NCT00080171). Our exposure was within‐day patterns of physical activity using a Multidimensional (14‐hour) Multilevel (4‐day) Functional Principal Component Analysis to analyze accelerometer data from analytic baseline. The outcome was all‐cause mortality assessed up to 8 years. Kaplan‐Meier survival curves and Cox Proportional Hazards regressions were used to calculate adjusted Hazard Ratios (aHR). Results There were 1927 adults with or at high risk for knee OA included in this analysis. We identified 4 primary within‐day activity patterns accounting for ~82% of sample variability. Participants who demonstrated low levels of activity in the morning and evening had 2.09 times the risk of mortality compared to those demonstrating the average activity pattern of the sample (aHR 2.09, 95% CI [1.15, 3.80]). Conclusion Unique within‐day patterns of physical activity were associated with mortality risk. Those with inactivity in the morning and evening were at increased risk for mortality.

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