The COVID-19 pandemic has created massive challenges for women’s employment. Women’s responsibilities were exacerbated by the closure of schools and child daycare facilities. Investigating the determinants of job losses among women is critical to avoiding dropouts and supporting re-entry into the labor market. This study investigates the factors driving women’s workforce losses during the pandemic in five Arab countries (Egypt, Tunisia, Morocco, Jordan, and Sudan). The current study focuses mainly on how COVID-19-induced responsibilities affected women’s employment during the pandemic. The study depends on the COVID-19 MENA Monitor Household Survey produced by the Economic Research Forum. The factor analysis of mixed data is used to construct the women’s responsibilities index that is made up of 18 variables. The mixed-effect logistic model is used to consider changes in working arrangements across economic activities. The results indicate that women with high family caregiving responsibilities were more likely to lose their jobs. Women working in the government sector and with health insurance were protected from job losses. Telecommuting played a significant role in helping women maintain their jobs. Work arrangements should be improved to consider increased unpaid domestic work. Family-friendly policies must be activated, and childcare leave must be facilitated and funded. The private sector should also be urged to improve workplace flexibility.