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The present prospective study examines the interplay between the quality of relationships with coworkers and work motivation in predicting burnout. Considering self‐determined motivation at work as a potential moderator, we investigated whether relationships with coworkers are equally important to all employees in preventing burnout. A total of 533 college employees participated in this study. Data were collected at two time points, two years apart. Results from structural equation modeling indicated negative main effects for high‐quality relationships and self‐determined motivation on burnout. A significant interaction effect between these two factors on burnout was also revealed, suggesting that high‐quality relationships with coworkers is crucial for those employees who exhibit less self‐determined work motivation. Implications for burnout research and management practices are discussed (Deci & Ryan, 1985 …