The effects of the pandemic on mental health can be studied through different variables, such as the number of COVID-19 stressors, the stressor types, and the stress responses. Understanding the sources of mental strain is crucial for developing effective interventions. The present study analyzed the relationship between these COVID-19-related variables and positive and negative mental health. A cross-sectional study was conducted with 666 individuals from the Portuguese general population, mostly females (65.5%) between 16–93 years old. They completed self-report measures regarding the number of COVID-19 stressors, the stressor types, the stress responses (IES-R), and positive (MHC-SF) and negative mental health (BSI-18). The results demonstrated that a higher number of COVID-19-experienced stressors and more stress responses were related to worse mental health. Regarding stressor types, experiences not related to the COVID-19 infection (e.g., tension at home) presented the largest effects on mental health. The strongest predictor was the stress responses for negative (β= 0.50) and positive mental health (β= −0.17). The predictors explained more about negative mental health than positive. These findings support the idea that individual appraisals play a crucial role in mental health.