Background: The rapid increase in confirmed cases of COVID-19 is placing a heavy burden on medical care systems. A case study of a tertiary referral medical center in central Taiwan was performed to present models for pain care for hospitalized patients with COVID-19. Methods: From August to December 2021, 32 adult hospitalized patients with COVID-19 were included in the study. The characteristics of pain experienced by patients and pain management were examined. Non-intubated patients completed the numeric rating scale. Regarding severely ill patients, the critical care pain observation tool (CPOT) was applied to assess their pain. The clinical decision support system, called 3324 system was implemented to improve pain management. Results: Thirty-two adult patients (15 men; 17 women) were included in the study, and 9 of them (28.1%) were intubated and required intensive care unit admission. Eleven patients (34.4%) experienced moderate pain or severe pain. The main causes of pain were headache, sore throat, and pain at upper trunk. Regarding severely ill patients, 6 patients had a CPOT score of ≥ 2. The number of cases in the present hospital’s 3324 system between May and July 2021 was not greater than the number of cases over the same period in 2020. Conclusions: At our hospital, nearly half of the hospitalized patients with COVID-19 experienced moderate to severe pain. Hence, the pain issue of confirmed cases of COVID-19 must be taken seriously. Although the pandemic caused changes in medical care, the hospital has been able to maintain its quality of care through the implementation of various pain monitoring and response measures. The findings demonstrate that promoting clinical decision support system and specialized case management can improve the quality of care.