Introduction: House officers who are suffering from stress, anxiety or depression are at risk of harm to themselves, colleagues and even patients, as well as affecting their livelihood. Objective: This study is aimed to find the prevalence of stress, anxiety and depression among house officers working in Kota Kinabalu, Sabah. Method: A cross-sectional study was done using a self-administered questionnaire containing socio-demographic factors and Depression, Anxiety and Stress Scale (DASS) 21. Results: Prevalence of stress, anxiety and depression were 57.1%, 63.7%, and 42.9% respectively. Multiple logistic regression analysis found that house officers who thought of quitting Housemanship was associated with stress (adjusted OR = 3.64, 95% CI: (1.44, 9.20), p = 0.006), and depression (adjusted OR = 8.26, 95% CI: (2.96, 23.02), p < 0.001). House officers who perceives that they are bullied is associated with anxiety (adjusted OR = 4.16, 95% CI: (1.33, 13.07), p = 0.015). Work experience of the house officers in months have a protective effect to stress (adjusted OR = 0.92, 95% CI: (0.87, 0.97), p = 0.004), anxiety (adjusted OR = 0.93, 95% CI: (0.88, 0.98), p = 0.006) and depression (adjusted OR = 0.92, 95% CI: (0.87, 0.98), p = 0.006). Conclusion: The prevalence of stress, anxiety and depression among house officers in Kota Kinabalu, Sabah is high. Management should look into the findings and understand the importance of addressing this problem as it may affect patient care and safety, and the livelihood of house officers. Future studies identifying why house officers are thinking of quitting service and why they do feel that they are being bullied may be warranted.