Background and Purpose: Breastfeeding has a vital role in ensuring the health of mother and infant, and ultimately the health of society. Breastfeeding self-efficacy is a strong predictor of the duration of breastfeeding, which in a variety of situations - including crises - may be affected by a number of factors. The aim of this study is to determine the predictors of breastfeeding self-efficacy in breastfeeding mothers during the Covid-19 pandemic.Materials and Methods: A cross-sectional study was conducted with the participation of 300 breastfeeding mothers whose children were breastfed during the Covid-19 pandemic. Sampling was based on convenience sampling and online method using a checklist of personal and social characteristics and breastfeeding self-efficacy questionnaires, spouse postpartum social support, perceived social support, anxiety and depression, and fear of Covid-19. Data were analyzed using Pearson correlation coefficient, one-way ANOVA and multi variable linear regression model via stepwise method. Significance level in this study was considered to be 0.05.Results: The mean breastfeeding self-efficacy score among participants was 58.19±10.48 (out of 70). Spouse postpartum social support (β = 0.732, p =0.04), intention to breastfeed (p = 0.001, β = 0.17), use of formula while breastfeeding (β = - 0.09, p<0.001), and depression (β = - 0.11, p<0.001), were predictors of breastfeeding self-efficacy. But fear of Covid-19 was not significantly correlated with breastfeeding self-efficacy (p = 0.514).Conclusion: The results of the present study showed that spouse postpartum social support and having the intention of breastfeeding with a positive effect; and depression and simultaneous use of formula in feeding the infant with a negative effect; are predictors of women’s breastfeeding self-efficacy during the Covid-19 pandemic. It seems that breastfeeding can be improved by counseling to improve receiving the spouse support, increasing the breastfeeding intent, and reducing the depression.