Workplace mental health is a cause for concern in many countries. Globally, 78% of the workforce experienced impairment of their mental health in 2020. In Japan, more than half of employees are mentally distressed. Previously, research has identified that self-compassion (i.e., being kind and understanding towards oneself) and work motivation were important to their mental health. However, how these three components relate to each other remains to be elucidated. Accordingly, this study aimed to examine the relationship between mental health problems, self-compassion and work motivation (i.e., intrinsic motivation, extrinsic motivation and amotivation). A cross-sectional design was employed, where 165 Japanese workers completed self-report scales regarding those three components. A correlation and path analyses were conducted. Mental health problems were positively associated with amotivation and negatively associated with age and self-compassion. While intrinsic motivation and extrinsic motivation did not mediate the impact of self-compassion on mental health problems, amotivation did. The findings can help managers and organizational psychologists help identify effective approaches to improving work mental health.