Small-to-medium enterprises (SMEs) may experience the antecedents and consequences of depression more acutely than larger organizations. Managing depressionrelated sickness absenteeism and presenteeism, and associated productivity loss may also be more challenging because the SME’s size and structure make administration, finance, and responsibilities of human resources difficult. This may diminish the growth and long-term sustainability of SME. However, the mental health of the SME workforce is a neglected sector in occupational health research and practice, despite the contribution it makes to developed economies worldwide. This study aims to review the literature on current stress, burnout, and depression, and uses existing knowledge of SME structure and characteristics to propose a theory as to why this may be the case. Further, using the information garnered, it developed a model to guide future research designed to test these assumptions, and inform the development of workplace mental health promotion programmes tailored to the needs of the SME sector.