Background: Seafarers are an occupational group amongst those at highest risk for stress, which may adversely affect their mental health. The primary aim of this study was to assess the effects of a psychosocial programme on perceived stress, resilience, and job satisfaction among a sample of merchant seafarers. Materials and methods: Secondary data analysis was conducted using a work questionnaire administered by a large shipping company. The matched subjects technique and multivariate analysis of covariance were conducted using a theoretical model of the programme’s effects on job satisfaction, resilience, and perceived stress. Results: A significant interaction between programme participation and weeks on board indicated that the effects of weeks on board on perceived stress differed significantly for the intervention group and matched control group. Weeks on board had a significant effect for perceived stress for the control group (p = 0.02), but not for the intervention group (p = 0.857). Conclusions: These findings indicate that participation in the programme moderated the effects of weeks on board on perceived stress, suggesting that the programme may have safeguarded participants against the effects of weeks on board on perceived stress. Importantly, however, a work environment that is experienced as supportive, inclusive and just is necessary as a cornerstone for individually-focused psychosocial interventions to be optimally applied.