Abrupt interruption in the performance of everyday occupations as a consequence of forced social distancing and home confinement, coupled with a lack of regulatory capacities and skills, can trigger harmful effects on people’s health and well-being. This study aimed to determine the factors related to the occupational balance in the Spanish population during home confinement as a consequence of the coronavirus disease 19 (COVID-19) pandemic. A total of 3261 subjects completed an online survey, which was disseminated through the mainstream social media platforms in Spain and included the Occupational Balance Questionnaire (OBQ), sociodemographic variables, and factors related to COVID-19 infection. The mean age of the participants (81.69% women) was 40.53 years (SD ± 14.05). Sociodemographic variables were related to a greater occupational balance, and the multivariate analysis showed that age (β = 0.071; p = 0.001), the perception of having received enough information (β = 0.071; p ≤ 0.001), not telecommuting (β = −0.047; p = 0.022), and not being infected by COVID-19 (β = 0.055; p = 0.007) contributed to a better occupational balance. There were profiles of people less likely to suffer disturbances in occupational balance during home confinement, but more studies are needed to help understand and analyze the effects of the COVID-19 pandemic on people’s occupational and mental health.