The recent outbreak of coronavirus disease 2019 (COVID-19) is the worst global crisis after World War II. Since the vaccine trials are still ongoing, the national lockdowns have been the most effective way to contain its spread. The pandemic has been extremely stressful and full of anxiety for those with comorbidities as they are the most vulnerable to the COVID-19 infections. Various efforts to assess and enhance the knowledge, attitudes, and practice, especially the high-risk groups, are critical to managing the COVID-19 pandemic successfully. A cross-sectional online survey was carried out using a self-designed questionnaire. A total of 383 participants who were 30 years or older, with at least one comorbidity, were included in the study. The mean age of the participants was 50.63±11.83 years. The most common comorbidities among the included participants were hypertension, followed by diabetes mellitus and thyroid disorders (48.5%, 44.7% and 23.3%, respectively). Our study also showed the education (p=0.004) and occupation (p=0.04) had a significant association with the attitude and practices towards the COVID-19 pandemic. In conclusion, our study showed that a high level of knowledge, attitude, and practices are the backbone to combat a global crisis like COVID-19.