Curiosity promotes focused engagement in novel and challenging situations and the accruement of resources that promote well-being. A critical open question is the extent to which curiosity lability, the degree to which curiosity fluctuates over short timescales, impacts well-being. We use data from a 21-day daily diary protocol as well as trait measures collected prior to the daily diary in 167 participants (mean age = 25.37 years, SD = 7.34) to test (i) the importance of curiosity lability for depression, flourishing, and life satisfaction, (ii) day-to-day associations among curiosity and happiness, depressed mood, anxiety, and physical activity, and (iii) the extent to which day’s mood acts as a mediator between day’s physical activity and day’s curiosity. Regression analyses indicate positive associations among curiosity lability and depression, as well as negative associations among curiosity lability and life satisfaction, above and beyond trait curiosity. No evidence for an association between curiosity lability and flourishing emerge when controlling for trait curiosity. Multilevel model results indicate that curiosity is higher on days of greater happiness and physical activity, and that curiosity is lower on days of greater depressed mood. We observe no association between curiosity and anxiety. Multilevel mediation models indicate evidence consistent with day’s depressed mood and happiness as mediators between physical activity and curiosity. In sum, we find that greater consistency in curiosity is associated with well-being, identify several sources of augmentation and blunting of curiosity in daily life, and provide support for purported mechanisms linking physical activity to curiosity via mood.