Background: Negative emotional effects were reported in different groups since the beginning of the COVID-19 pandemic. However, few studies compare those groups regarding the emotional effects of the COVID-19. To this end, this study's main objective is to compare the emotional effects of the COVID-19 between three different groups, namely health personnel, medical students, and the general population sample.Methods: We recruited 375 participants for this study, of which 125 were medical students (preclinical studies = 59, clinical studies = 66), 125 were health personnel (COVID-19 first-line personnel = 59, personnel not related with COVID-19 = 66), and 125 belonged to the general population. PHQ-9 (depression), GAD-7 (anxiety), and CPDI (COVID-19 related stress) were assessed to measure the emotional impact. A multinomial logistic regression was carried out to measure differences between groups, considering possible confounding factors. Results: Regarding CPDI values, all other groups showed reduced CPDI values compared to COVID-19 first-line personnel. However, the general population, preclinical medical students, and clinical medical students showed increased PHQ-9 values compared to COVID-19 first-line personnel. Finally, confounder factors, gender and age, correlated negatively with higher CPDI and PHQ-9 scores. Conclusions: Being COVID-19 first-line personnel is associated with more stress related to COVID-19. Depression is associated, however, with other groups not directly involved with the treatment of COVID-19 patients. Female and younger age participants correlated with depression and stress related to COVID-19.