Background Nursing has a reputation for being one of the most stressful occupations. As a result of their work, many nurses suffer from anxiety and depression. Nurses are also at risk of poor sleep owing to their work nature. This study aimed to examine the relationship between work–family conflict, sleep quality, and depressive symptoms among mental health nurses. A descriptive cross-sectional study design was utilized in this study. Setting/sample: This study was conducted at El Azazi Hospital for Mental Health, Al-Sharkia Governorate on 139 mental health nurses. Four tools were used in this study: Socio-demographic data sheet, Work–Family Conflict Scale, Arabic Pittsburgh Sleep Quality Index, and Arabic Center for Epidemiologic Studies Depression Scale. Results Results revealed that, a significant percentage of mental health nurses suffered from poor sleep quality and depressive symptoms, there were highly statistically significantly positive correlations between work–family conflict (WFC) and both of Pittsburgh Sleep Quality Index (PSQI) and depressive symptoms among nurses. Conclusions Working with psychiatric patients affected their nurses, which disturbed their sleep quality and led to depressive symptoms. As well, increasing work–family conflict in mental health nurses leads to poor sleep quality and depressive symptoms. Family interference with work, sleep quality, and work interference with family were statistically significant predictors of depressive symptoms.