Background <p>The high prevalence of mental health issues (MHI) among employees poses significant societal challenges. However, little is known about factors that influence their ability to remain employed, maintain productivity, and thrive at work.</p> Objective <p>This study examines differences in occupational health outcomes (burnout, work engagement, and work ability) between employees with and without MHI and the applicability of the Job Demands-Resources model (including job demands, job resources as psychosocial working conditions and sense of coherence (SOC) as a personal resource) among employees with MHI, while particularly controlling for disease-specific factors.</p> Methods <p>Pooled data from two measurement waves were analyzed, including employees with current MHI (<i>N</i> = 92) and those without MHI (<i>N</i> = 877) from German-speaking countries. Mixed-effects models examined relationships between sociodemographic, disease-specific factors, psychosocial working conditions, SOC, and occupational health outcomes.</p> Results <p>Employees with MHI showed lower occupational health levels (higher burnout, reduced work ability) than those without. Among employees with MHI, SOC and job resources were significantly associated with all occupational health outcomes, while job demands primarily predicted burnout. Sickness absence correlated negatively with both burnout and work ability. The association between SOC and work ability was stronger for employees with MHI than for those without.</p> Conclusions <p>Job resources and SOC play a role for occupational health in employees with MHI. Targeted interventions to strengthen these resources should be prioritized.</p>