In 2018, standard 035 (known in Spanish as NOM-035-STPS-2018) was published in the Official Gazette of the Federation. Such standard evaluates Psychosocial Risk Factors (PRF) in Mexican workers to promote their job well-being. In 2020, COVID-19 changed the work practices of universities and companies in Mexico. Therefore, their analysis is timely and relevant. The objective of this study was to compare the PRFs among workers at the Universidad Autonoma de Nuevo Leon in two conditions: pre-pandemic office and home office during social distancing due to COVID-19, and to identify the relationship between gender and modality with the psychosocial risk. Consequently, the instrument was administered through two modalities, one test was administered in the office environment in November 2019, prior to the COVID-19 pandemic, and the other in remote work in June 2020, at the beginning of social distancing. The results showed that performing tasks in the office environment generates a high general psychosocial risk, while home office is a medium general risk, according to NOM-035. However, the statistical analysis did not show a significant difference (P < 0.05) in general risk between both work contexts, nor in the comparison of risk between genders. Nonetheless, in the analysis of the categories and domains that make up psychosocial risk, a significant difference (P < 0.05) was found between some of them. Men presented a higher risk in the office in the category of leadership and job relations, which decreased (P < 0.05) due to the effect of home office. The presence of psycho-social risk reported by some of the workers in different categories and domains indicated the need to implement policies that reduce these risks, considering both work modality and gender. This will allow, in addition to complying with NOM-035, to improve the quality of the job well-being of workers.