During the COVID-19 pandemic, persons under surveillance (PUS) were isolated in quarantine centres instead of at home. However, there is limited knowledge regarding the mental health issues experienced by these persons. This study aimed to assess mental health outcomes and associated factors among PUS and frontline workers at quarantine centres. This study conducted an analysis of secondary data from a cross-sectional survey carried out by the Mental Health and Psychosocial Support Services (MHPSS). The MHPSS employed the Depression, Anxiety, and Stress Scale (DASS-21) to evaluate mental health outcomes across 49 quarantine centres in Malaysia. The study included a total of 4577 respondents. The prevalence of stress, anxiety, and depression was found to be 0.9%, 11.4%, and 10.2%, respectively. Frontline workers and being part of the younger age group were found to be associated with depression, anxiety, and stress. Other factors associated with mental health issues were being female, staying at an institution-type centre, and a longer duration of the stay or work at the centre. In conclusion, assessing the mental health status and its associated factors among quarantine centre occupants is crucial for developing future strategies to safeguard their mental well-being.