Background: The aim of the study is to compare the emotional effects of COVID-19 among three different groups, namely: health personnel, medical students, and a sample of the general population. Methods: 375 participants were recruited for this study, of which 125 were medical students (preclinical studies, 59; clinical studies, 66), 125 were health personnel (COVID-19 frontline personnel, 59; personnel not related with COVID-19, 66), and 125 belonged to the general population. The PHQ-9, GAD-7, and CPDI scales were used to assess the emotional impact. A multinomial logistic regression was performed to measure differences between groups, considering potential confounding factors. Results: Regarding CPDI values, all other groups showed reduced values compared to COVID-19 frontline personnel. However, the general population, preclinical and clinical medical students showed increased PHQ-9 values compared to COVID-19 frontline personnel. Finally, confounding factors, gender and age correlated negatively with higher CPDI and PHQ-9 scores. Conclusions: Being frontline personnel is associated with increased COVID-19-related stress. Depression is associated, however, with other groups not directly involved with the treatment of COVID-19 patients. Female gender and younger age correlated with COVID-19-related depression and stress.