This study aimed to explore the socio-demographic characteristics, mental health status, and perceived causes of pandemic fatigue with COVID-19 pandemic fatigue among the general population of Malaysia. The data was collected online during the transition from the COVID-19 pandemic phase to the endemic phase in Malaysia from 1 to 30 April 2022. Sociodemographic data, Depression Anxiety Stress Scale-21 (DASS-21), perceived causes of pandemic fatigue, and the Fatigue Assessment Scale (FAS) were included in the survey. The chi-square test and a simplelogistic regression analysis were used to identify predictors of pandemic fatigue. The completed survey (N = 775) included individuals aged 18 years or above [mean 31.98 (SD = 12.16)] from all states in Malaysia. Pandemic fatigue prevalence was 54.2%. Severe to extremely severe depression, anxiety, and stress symptoms were detected in 11.2%, 14.9%, and 9.1% of the participants, respectively. Younger age, non-Malay ethnicity, living alone, and higher income categories were significantly higher in the fatigued group. Higher DASS-21 scores on all domains were associated with higher FAS scores. Meanwhile, high scores for perceived tiredness from complying with the COVID-19 Standard Operating Procedure (SOP), perceived risk of infection from COVID-19, perceived hardship due to the pandemic, perceived public complacency during the pandemic, and perceived changes due to the pandemic were associated with a higher FAS score. This study provides valuable information for policymakers and mental health professionals worldwide on pandemic fatigue and its associated factors, including mental health status in Malaysia.