The COVID-19 pandemic has created and exacerbated emotional, financial, and technical challenges for informal caregivers of older people. The aim of this study was to explore the caregiving situation and subjective burden of informal caregivers of older family members during COVID-19, and to investigate how a caregiving situation’s characteristics predict the subjective burden of care in times of COVID-19. The study was conducted in April and May 2021 via an online access panel. The sample (n = 612) was determined using a screening test that enabled us to focus on a Slovenian population of informal caregivers aged 40+ caring for a person aged 65+ for at least four hours/week on average. Our findings reveal that the subjective burden of care was high among informal caregivers during COVID-19. Multiple regression analysis showed that the provision of activities of daily living, care duration, average hours of care per week, formal care status, and recipients’ health problems related to dementia or other memory problems significantly predicted the subjective burden of caregivers. These findings call for better recognition of the role of informal caregivers. The time and effort devoted to informal care should be supported by legislation and social security.