This article explores the socio-labor conditions in which people worked during confinement, analyzing the predictors of work-related stress, according to work modality (face-to-face or teleworking), from a holistic and quantitative (N = 328) point of view. To identify predictors of stress, correlational analyses and multiple hierarchical regressions were conducted with individual, organizational, and societal variables. Furthermore, to analyze the possible modulating role of gender, caregiving, and the level of responsibility in organizations in the relationship between predictor variables and work stress, the macro process of Hayes et al. (2017) was used. Our results show that work–family conflict and ruminative thoughts predict stress in both modalities. In teleworking modality, the hours dedicated to work predicted stress, and in face-to-face modality, safety measures and perceived economic threat (tendentially). Being in charge of persons moderated the relationship between ruminative thoughts and economic threat, and stress in face-to-face. Results are discussed by identifying good practices that can improve workplace risk prevention strategies.