Moral distress – such as feeling strong regret over difficult patient situations – is common among nurses and physicians. Regret intensity, as well as the coping strategies used to manage regrets, may also influence the health and sickness absence of healthcare professionals. The objective of this study was to determine if the experience of regret related to difficult care-related situations is associated with poor health and sick leave and if coping strategies mediate these associations. Two cross-sectional surveys were conducted in Switzerland (Geneva, 2011 and Zurich, 2014). Outcomes were self-rated health (SRH) and sick leave in the last 6 months. We examined the associations of regret intensity with the most important care-related regret, number of recent care-related regrets, and coping strategies, using regressions models. Among 775 respondents, most reported very good SRH and 9.7% indicated absence from work during four working days or more. Intensity of the most important regret was associated with poor SRH among nurses and physicians, and with higher sick leave among nurses. Maladaptive emotion-focused strategies were associated with poor SRH among nurses, whereas adaptive emotion-focused strategies were positively associated with higher SRH and lower sick leave among physicians. Because care-related regret is an integral part of clinical practice in acute care hospitals, helping physicians and, especially, nurses to learn how to deal with negative events may yield beneficial consequences at the individual, patient care, and institutional level.