Mental health nurses have traditionally lagged in terms of physical healthcare skills and have been found to have poorer cultural safety-related attitudes relative to other nurses. Organizational culture, including safety-related culture, is associated with important aspects of care quality. The aim of the current study was to examine the relationships between safety-related attitudes, physical healthcare-related knowledge and organizational culture among mental health nurses. By doing so, the intention was to inform decisions about interventions to improve attitudes and care related to severe physiological deterioration among mental health nurses. The study design was cross-sectional and correlational. The safety-related attitudes of N = 133 nurses from the inpatient mental health services of one Local Health District in New South Wales, Australia, were examined in terms of a range of potential predictor variables of safety attitudes (Safety Attitudes Questionnaire) including individual organizational-perceiver type (Organisational Climate Assessment Inventory), knowledge of emergency medical healthcare (Lambeth In situ Training Questionnaire), use and perception of medical emergency teams (purpose-designed questionnaire) and a range of demographic variables. Regression analyses revealed that those who perceived the organization to have a primarily market-oriented culture had poorer safety-related attitudes than those who perceived a more clan-type culture. Number of years qualified was negatively associated with safety attitudes. To our knowledge, this is the first study in mental health which demonstrates a link between organizational culture-perception and safety attitudes related to physical healthcare. Results suggest that, among nurses, individuals have quite different perceptions of the organizational culture. In turn, this suggests that the ‘one-size fits all’ approach to changing organizational culture may be inappropriate.