BackgroundIn this study, we analyze the association of social isolation in the first phase of the pandemic with perceived stress among residents of Poland and Italy with a look at how these populations adjust to and comply with implemented regulations, guidelines, and restrictions.Materials and MethodsInternet survey with Perceived Stress Scale (PSS-10) and questions regarding mobility patterns, attitude, and propensity to adjust toward the implemented measures and current health condition was made among Polish and Italian residents (Cronbach’s alpha 0.86 and 0.79, respectively). The sample size was 7,108 (6,169 completed questionnaires in Poland and 939 in Italy).ResultsThe Polish group had a higher stress level than the Italian group (mean PSS-10 total score 22,14 vs 17,01, respectively; p < 0.01). There was a greater prevalence of chronic diseases among Polish respondents. Italian subjects expressed more concern about their health, as well as about their future employment. Italian subjects did not comply with suggested restrictions as much as Polish subjects and were less eager to restrain from their usual activities (social, physical, and religious), which were more often perceived as “most needed matters” in Italian than in Polish residents.ConclusionHigher activity level was found to be correlated with lower perceived stress, but the causality is unclear. Difference in adherence to restrictions between Polish and Italian residents suggests that introducing similar lockdown policies worldwide may not be as beneficial as expected. However, due to the applied method of convenience sampling and uneven study groups, one should be careful with generalizing these results.