The present study examines the role of daily difficulties in emotion regulation at work in nurse’s daily well-being and how certain job resources and recovery experiences influence this relationship. We hypothesized that daily difficulties to regulate emotions at work would be significantly and positively related to emotional exhaustion at work in the afternoon, and to fatigue and negative affect at home at night. Moreover, we hypothesized that coworker and supervisor support and psychological detachment and relaxation would buffer the negative impact of these difficulties on the outcomes. Nurses (N = 74) from various Spanish hospitals and primary health care centers completed a general questionnaire and a diary booklet over 5 consecutive workdays at 2 different moments, after work and at night (N = 370 observations). The results of multilevel analyses showed that nurses’ daily difficulties in emotion regulation have a direct effect on daily emotional exhaustion at work, and on fatigue and negative affect at home at night. We also found that coworker support, psychological detachment and relaxation minimize the unfavorable effects on well-being of difficulties in emotion regulation. Limitations and implications for nursing and other health occupations are mentioned.