Purpose: Covid-19 pandemic increased the use of e-learning and the ensuing academic stress. This research aims to study the relationship between e-learning induced academic stress and academic self-efficacy in the Yazd branch of Payame Noor University in Iran. Methodology: This is a descriptive-correlational study. The study population was the Yazd branch of Payme Noore University students in the 2020-21 academic year. Cochran’s formula gave us a sample size of 319 people. Due to the Covid-19 pandemic and the unavailability of some of the sample members, we used voluntary sampling. Our research tools were the academic stress scale (Pooladi Reyshahri, 1995) and the academic self-efficacy scale (Owen and Froman, 1988). We sent the scale to the subjects electronically. The scales’ alpha Cronbach reliabilities were 0.90 and 0.84, respectively. We analyzed the data using the T-test, correlation, and regression in SPSS version 21. Findings: Our findings showed that e-learning induced academic stress, and its subscales (academic conditions and economic environment stresses) were significantly below average in the students. Students’ academic stress and academic self-efficacy were significantly and inversely related. Academic stress could significantly explain self-efficacy (P < .001). Conclusion: Our results showed the negative role of academic stress in explaining students’ academic self-efficacy. Reducing students' academic stressors through academic workshops can significantly increase academic self-efficacy.