The abrupt onset of COVID-19, with its rapid spread, has had brutal consequences in all areas of society, including the workplace. In this paper, we report the working conditions, health, and tranquilisers and opioid analgesics use of workers during the first months of the ensuing pandemic, according to whether they were frontline workers or not and also according to sex. Our analysis is based on cross-sectional survey data (collected during April and May 2020) from the wage-earning population in Spain (n=15 070). We estimate prevalences, adjusted prevalence differences and adjusted prevalence ratios by sex and according to whether the worker is a frontline worker or not. Employment and working conditions, exposure to psychosocial risks, as well as health status and the consumption of tranquilisers and opioid analgesics all showed sex and sectoral (frontline vs non-frontline) inequalities, which placed essential women workers in a particularly vulnerable position. Moreover, the consumption of tranquilisers and opioid analgesics increased during the pandemic and health worsened significantly among frontline women workers. The exceptional situation caused by the COVID-19 pandemic provides an opportunity to revalue essential sectors and to dignify such employment and working conditions, especially among women. There is an urgent need to improve working conditions and reduce occupational risk, particularly among frontline workers. In addition, this study highlights the public health problem posed by tranquilisers and opioid analgesics consumption, especially among frontline women.