This study examined the moderating effect of nursing practice environment on the relationship between clinical nurses' sleep quality and wellness. The wellness of clinical nurses is a direct outcome of individual-level health behaviors and organizational environmental factors. This study was a cross-sectional analysis. Participants were clinical nurses recruited using convenience sampling. The Nurse Practice Environment Scale, Wellness Index, and Pittsburgh Sleep Quality Index, Korean version (PSQI-K) were used. Data collected from 1874 nurses were analyzed using descriptive statistics and hierarchical multiple regression analyses. A total of 95.3% of the participants were women, and the mean age was 28.8 years. Further, 42.4% of the participants had a nursing career of 5 years or longer. The mean score for nursing practice environment was 2.24 and the mean PSQI-K score was 9.39. Nurses with less than 1 year of experience reported lower wellness scores. The wellness scores decreased with poorer sleep quality, and a more positive evaluation of the nursing practice environment predicted higher levels of wellness. Nursing practice environment had a moderating effect on the negative association of nurses' poor sleep quality with their wellness. Regarding management, individual strategies for nurses' well-being and organizational improvement policies may improve the nursing work environment.