Biomedical waste (BMW) management is an essential practice of healthcare professionals (HCPs) for preventing health and also environmental hazards. Coronavirus disease (COVID-19) has become a global pandemic, posing significant challenges for healthcare sectors. A cross-sectional study was performed to assess the knowledge, practice, and attitude on BMW management among HCPs when taking care of patients with COVID-19 and associated with demographic variables. From Al-Ahsa healthcare sectors, 256 HCPs were selected randomly, of which 105 (41%) had excellent knowledge, 87 (34%) had good knowledge, and 64 (25%) had poor knowledge with a mean score of 13.1 +/- 3.6. A higher mean score was (14.4 +/- 3.2) obtained by physicians, and (13.6 +/- 3.8) nurses than the other HCPs. Regarding practice, 72 (28.1%) HCPs used and discarded PPE while handling biomedical wastes. Additionally, 88 (34.4%) followed proper hand hygiene before and after each procedure and whenever needed. Physicians, nurses, and respiratory therapists had a more favorable attitude than other HCPs. There was a statistically significant association found among knowledge level and educational qualification (p < 0.0001), gender (p < 0.001), and work experience (p < 0.05). Emphasis is needed to train all HCPs regarding proper BMW management during this pandemic to prevent infection transmission.