The COVID-19 pandemic globally impacted physical, spiritual, and mental health (MH). The consequences significantly affected students' quality of life (QoL) too. This cross-sectional study assessed MH status and its relationship to the QoL of college students in Indonesia. This study collected data (September 2021-April 2022) online using the depression, anxiety, and stress scale-21 (DASS-21) to measure MH and the world health organization quality-of-life scale (WHOQoL-BREF) to measure the QoL. The data were analysed using SPSS with a bivariate and multivariate linear regression test. A total of 606 respondents participated in this study, with the majority being women (81.0%), aged 21-27 years (44.3%), and unmarried (98.5%) respondents. We observed 24.4% (n = 148) moderate depression, 18.3% (n = 111) very severe anxiety, and 21.1% (n = 128) moderate stress status. The QoL measurement determined that a moderate QoL in the physical and environmental health domains (>70%) and poor QoL in the psychological health domain (58.3%) were found. Gender, age, family support, history of COVID-19 diagnosis, family with COVID-19 diagnosis, vaccination status, and physical symptoms are significantly associated with MH status and QoL (p-value < 0.05). This study demonstrated that COVID-19 was negatively related to college students' MH and QoL. Targeted interventions may be needed to ameliorate both MH and QoL.