Abstract Purpose To assess gender differences in COVID-19 related changes in home and work responsibilities longitudinally, and determine whether these differences, together with other potential risk and protective factors, are associated with depression, anxiety, and post-traumatic stress disorder (PTSD) symptomatology. Method Symptoms of depression, anxiety, and PTSD were measured using an online survey instrument, between May 2020 and April 2021, in four waves completed at 3-monthly intervals. Analyses were based on data from the COvid MEntal healTh (COMET) survey which investigated the mental health effects of the COVID-19 outbreak spanning 13 countries on five continents in N = 7,909 participants. Results From the first to the last wave, women reported a greater increase in home and work responsibilities, and had higher depression, anxiety and PTSD scores compared to men. Women who reported a reduction in income due to the pandemic had higher depression scores. Working harder and experiencing a reduction in income were also associated with higher anxiety scores in women but not in men. Women were more likely to score above the cut-off for depression (32.5% vs 23.6%, p < .001), anxiety (21.2% vs 14.4%, p < .001) and PTSD (21.2% vs 14.4%, p < .001) than men during the first wave. Stronger reliance on socially supported coping mechanisms was a risk factor for depression, anxiety and PTSD in men and women. Conclusion Women were more likely to report mental health problems which may be related to the gender disproportionate increase in home and work responsibilities but not necessarily due to COVID-19 stressors.