Female migrant domestic workers face precarious conditions, yet little is known about the impact of this work on their health. This study extends the JD-R model’s health impairment process to Ugandan female migrant domestic workers in Saudi Arabia. Data were collected before leaving Uganda and through a biweekly diary method across four times (Nparticipants = 185, Nobservations = 403). Results showed that family demands positively predicted emotional exhaustion but not somatic complaints. Unexpectedly, work pressure and sexual harassment did not predict either outcomes. Job autonomy negatively predicted both emotional exhaustion and somatic complaints, whereas social support had a positive effect. Core self-evaluation (CSE) moderated the link between autonomy and emotional exhaustion, highlighting the importance of individual characteristics. These findings emphasize the need to address job demands and redesign migrant domestic work to enhance autonomy. Our study provides a foundation for further research on migrant domestic workers’ well-being.