The COVID-19 pandemic has increased social and emotional stressors globally, increasing mental health concerns and the risk of psychiatric illness worldwide. To date, relatively little is known about the impact of the pandemic on vulnerable groups such as women and children in low-resourced settings who generally have limited access to mental health care. We explore two rounds of data collected as part of an ongoing trial of early childhood development to assess mental health distress among mothers of children under 5-years-old living in two rural areas of Zambia during the COVID-19 pandemic. We examined the prevalence of mental health distress among a cohort of 1105 mothers using the World Health Organization’s Self-Reporting Questionnaire (SRQ-20) before the onset of the COVID-19 pandemic in August 2019 and after the first two infection waves in October-November 2021. Our primary outcome was mental health distress, defined as SRQ-20 score above 7. We analyzed social, economic and family level characteristics as factors modifying to the COVID-19 induced changes in the mental health status. At baseline, 22.5% of women were in mental health distress. The odds of mental health distress among women increased marginally over the first two waves of the pandemic (aOR1.22, CI 0.99–1.49). Women under age 30, with lower educational background, with less than three children, and those living in Eastern Province (compared to Southern Province) of Zambia, were found to be at highest risk of mental health deterioration during the pandemic. Our findings suggest that the prevalence of mental health distress is high in this population and has further worsened during COVID-19 pandemic. Public health interventions targeting mothers’ mental health in low resource settings may want to particularly focus on young mothers with limited educational attainment.