Introduction: The COVID-19 pandemic had a great impact on everyday life in Croatia. The first wave of the pandemic pertains to the period from March to June 2020, while the second wave of the pandemic refers to the period from August 2020 to February 2021. In addition, the country was affected by the Zagreb earthquake during the first wave, and the Petrinja earthquake during the second wave. Objective: Comparison of mental distress, substance abuse, and changes in habits during the first and second wave of the COVID-19 pandemic, along with research into the predictors of distress. Respondents and methodology: The survey was conducted during two waves of the COVID-19 pandemic through an online questionnaire. During the first wave, data was collected for 2375 respondents, while it was gathered for 1312 respondents during the second wave. The COV-19 – Impact on Quality of Life Scale (COV-19-QoL), assessment of mental distress using the Depression, Anxiety and Stress Scale (DASS-21) and Insomnia Severity Index (ISI), questionnaire on changes in habits and addictive behavior, questionnaire on social support, Brief Coping Orientation to Problems Experienced (BRIEF-COPE), Connor-Davidson Resilience Scale (CD-RISC) and the Toronto Alexithymia Scale (TAS-20) were used. Results: Mental distress measured by the DASS and ISI scales in the second value was higher compared to the first (p<0.001). When assessing substance abuse, we found a statistically significant increase of consumption of sedatives (p<0.001) and reduced alcohol consumption (p<0.001) in the second wave of the COVID-19 pandemic compared to the first. There was no statistically significant difference for the consumption of marijuana, psychoactive substances, and opiate drugs, while the statistically significant reduction in the use of tobacco had a weak association. Predictors for depression-DASS and stress-DASS were lower social support (family), unemployment, a higher TAS and COVID-19 scale score, with a lower score on the CD-RISC-10 scale. Predictors for anxiety-DASS and insomnia were reduced social support (family), and a higher score on the alexithymia and COVID-19 scales, with a lower score on the CD-RISC-10 scale. An additional predictor for stress-DASS and anxiety-DASS was reduced social support (significant other). Conclusion: There is a visible need for planning a care system that would strengthen community support to reduce distress in pandemic situations, while adapting it to individualized needs defined by the level of vulnerability to stress.