In 2021, the expenses paid by households worldwide due to COVID-19 showed an increasing behavior and directly affected economic income since they were part of unforeseen expenses among households and became a factor that contributed to the increase in the levels of poverty mainly in households that were not part of the health system. The objective of this research was to establish the main determinants of out-of-pocket spending on health in Peruvian households in the times of the pandemic. A quantitative approach, of a nonexperimental type, with a descriptive and correlational methodological design was considered. The database of the National Household Survey of the National Institute of Statistics and Informatics for 2021 was used as a source of information, applying the binomial logit econometric model. Out-of-pocket expenses during the pandemic compared to normal periods were shared by the members of the households. Since they were part of unforeseen expenses, these expenses mainly impacted the heads of the households and strongly affected household budgets. For this reason, the type of insurance, the suffering of household members from a disease, the results of tests for COVID-19, the expenditure on individual health, the existence of permanent limitations to any member of the household, the presence of an older adult in the household, and the marital status of the head of the household determined and positively influenced out-of-pocket spending in households in Peru with 36.85, 8.48, 6.50, 0.0065, 23.73, 16.79, and 2.44 percentage units. However, the existence of a drinking water service in the household, educational level, and the area of residence determined and negatively influenced out-of-pocket spending in households in Peru with 4.81, 6.75, and 19.26 percentage units, respectively. The type of insurance, the suffering of an individual from a disease, the results of COVID-19 tests, health spending, the existence of permanent limitations, the presence of an older adult in the household, and the marital status of the head of the household positively determined out-of-pocket spending in households in Peru, while the existence of a potable water service, educational level, and the area of residence determined out-of-pocket expenses in a negative or indirect way.