Background: Mental health is one of the principal indicators of people's quality of life. One of the professions most commonly associated with mental health problems is nursing. Objectives: We analyzed mental health in a group of female and male nurses from a hospital in Madrid (Spain) to evaluate whether differences exist between the groups. Furthermore, there is an analysis regarding whether the variables affecting mental health in female nurses are different from those affecting male nurses. Patients and Methods:The research is non-experimental, observational, with a cross sectional and descriptive analysis. The GHQ-12 instrument was chosen for the analysis of mental health in male and female nurses. The GHQ-12 has been validated in the Spanish population. Results: Male and female professional nurses scored worse in mental health than the population as a whole. Female nurses had worse scores than male nurses. Mental health in male nurses is related to age, self-perceived health, stress at work, and job satisfaction. The variables related to mental health in female nurses are stress at work and rest/sleep. Conclusions: The variables explaining the state of mental health in female and male nurses are different. The only variable in both regression equations is stress at work, and even then it has different magnitudes for male and female nurses. An awareness of possible quantitative and qualitative differences in the mental health of male and female nurses will contribute to the optimal design of more efficient, evidence-based treatments geared to improving the health of these professionals.