Background Social isolation is ongoing worldwide with the aim to stem the spread of the novel coronavirus SARS‐CoV‐2 responsible for the COVID‐19 pandemic. However, social isolation leads to significant psycho‐emotional changes. This study aimed to assess the effect of distance education (DE) activities implemented due to social isolation, on the quality of life of undergraduate dentistry students. Method An e ‐questionnaire (Google Forms®) was administered to identify specific DE activities after social isolation and included the World Health Organization Quality of Life (WHOQOL)‐bref questionnaire. The e ‐questionnaire was sent 14 days after the initiation of social isolation, remaining available for 48h. Cronbach’s alpha and the means of the quality of life domains were calculated and analyzed using the Friedman/Dunn and Spearman’s correlation tests. After ranking, Chi‐squared and Fisher’s exact tests plus multinomial‐logistic‐regression were performed (SPSS, p<0.05). Result There was an excellent internal consistency of WHOQOL‐bref (α=0.916), and the mean quality of life (0‐100) was 70.66±12.61. The psychological domain was the most affected (p<0.001). The social domain exhibited the weakest correlation with overall quality of life (p<0.001, r=0.688). The use of the Internet, cell phones, and streaming media increased, although all students had DE activities. In the multivariate analysis, attending virtual meetings (p=0.028) and performing DE activities in an office/study room (p=0.034) were significantly associated with good quality of life. Conclusion Facing social isolation never previously experienced by this generation, undergraduate dentistry students are at risk of reduced quality of life. Therefore, performing DE activities through devices with teacher‐student interaction is a key coping tool.