Background: The Covid-19 pandemic is associated with adverse mental health outcomes for people worldwide. Objective: The study aimed to assess mental health during the Covid-19 pandemic and the key risk factors from the human ecology perspective in Croatia’s adult population. Method: An online panel survey with 1, 201 adult participants (50.1% women) was done with a nationally representative sample in terms of gender, age, and country region four months after the nation lockdown began and two months after most of the restrictions were lifted. Indicators of mental health included symptoms of adjustment disorder (ADNM-8) ; depression, anxiety, and stress (DASS-21) ; symptoms of post- traumatic stress disorder (PC-PTSD-5) ; and well-being (WHO-5). Results: In the entire sample, 9.8% (95% confidence interval [CI]: 7.9%, 14.0%) of the participants were at risk of adjustment disorder, 7.7% (95% CI: 6.7%, 11.9%) were at risk of depression disorder, and 7.8% (95% CI: 5.3%, 10.3%) were at risk of anxiety disorder. In addition, 7.2% (95% CI: 5.3%, 10.2%) were experiencing high levels of stress. The average well-being score was 56.5 (SD = 21.91) on a scale from 0 to 100. Among the participants who have lifetime traumatic experience (n = 429), 14% (95% CI: 10.6%, 17.2%) were at risk for PTSD. Key risk factors for specific mental health outcomes differed, but the common ones included: current health status, previous mental health diagnosis, and psychological resilience. Being younger, having a below-average income, and excessively following news about Covid-19 were predictive for some of the mental health problems. Conclusions: Together, the key risk factors identified in this study indicate the need for public health interventions addressing the general population’s mental health, but also for specific risk groups. Lower rates of mental health symptoms assessed soon after lifting quarantine measures that have been found in other studies may indicate human resilience capacity.