Background: The coronavirus disease 2019 (COVID-19) caused many adverse effects, including increased stress in patients. The present study aimed to determine the effect of an online self-care training program on perceived stress in COVID-19 patients.Methods: This quasi-experimental study was fulfilled by recruiting 132 COVID-19 patients, referred to two hospitals in Isfahan, Iran, from February 20 to August 22, 2021. These patients were selected using the convenience sampling method, and were then randomized into experimental (n=63) and control (n=63) groups. The online self-care training program was subsequently presented to the patients in the experimental group, during six sessions of 30 minutes for two weeks. E-learning and educational content introduced through lectures, multimedia, and instructional videos using web platforms. Then, daily follow-up sessions continued until one month after the intervention. The data were collected administering an individual characteristic form and the Perceived Stress Scale (PSS) at three stages before, immediately, and one month after the intervention.Results: The mean scores of perceived stress before, immediately, and one month after the intervention in the experimental group were respectively 30.51±6.31, 24.59±4.66, and 26.57±3.82, and they were 29.78±4.81, 29.4±4.57, and 29.11±4.73 in that order in the control group. Moreover, no significant difference was observed between both groups at the pre-intervention stage (p=0.467), while the mean scores of perceived stress in the experimental group were lower compared with those in the control group immediately (p<0.001) and one month after the intervention (p=0.001). The mean scores of perceived stress in the experimental group before, immediately, and one month after the intervention had also changed in a significant manner (p<0.001), whereas there was no significant variation in the control group in this respect (p=0.298).Conclusions: The online self-care training program led to a reduction in perceived stress in COVID-19 patients. It is thus recommended to implement this cheap, safe, and efficient method to relieve perceived stress in such cases.