This study aims to assess changes in long-term care (LTC) residents’ quality of life (QoL) before and during the COVID-19 pandemic. A pre-test post-test study of 49 QoL measures, across four dimensions from the interRAI self-reported QoL survey, was conducted. Secondary data from 2019 (n = 116) and 2020 (n = 128) were analysed to assess the change in QoL. A significant decline in 12 measures was observed, indicating a change in QoL of LTC residents during the pandemic. Social life was the dimension mostly affected with residents reporting less opportunities to spend time with like-minded residents, explore new skills and interests, participate in meaningful religious activities, and have enjoyable things to do in the evenings. Several measures of personal control, staff responsiveness and care, and safety also demonstrated a significant change. The results can inform future strategies for pandemic and outbreak preparedness. Balancing the safety of residents with attention to their QoL should be a priority moving forward.