Personal protective equipment (PPE) pollution has become one of the most pending environmental challenges resulting from the pandemic. While various studies investigated PPE pollution in the marine environment, freshwater bodies have been largely overlooked. In the present study, PPE monitoring was carried out in the vicinity of Lake Tana, the largest lake in Ethiopia. PPE density, types, and chemical composition (FTIR spectroscopy) were reported. A total of 221 PPEs were identified with a density ranging from 1.22 × 10−5 PPE m−2 (control site S1) to 2.88× 10−4 PPE m−2 with a mean density of 1.54 × 10−4 ± 2.58 × 10−5 PPE m−2. Mismanaged PPE waste was found in all the sampling sites, mostly consisting of surgical face masks (93.7%). Statistical analyzes revealed significantly higher PPE densities in sites where several recreational, touristic, and commercial activities take place, thus, revealing the main sources of PPE pollution. Furthermore, polypropylene and polyester fabrics were identified as the main components of surgical and reusable cloth masks, respectively. Given the hazard that PPEs represent to aquatic biota (e.g., entanglement, ingestion) and their ability to release microplastics (MPs), it is necessary to implement sufficient solid waste management plans and infrastructure where lake activities take place. Additionally, local authorities must promote and ensure sustainable tourism in order to maintain the ecosystems in Lake Tana. Prospective research priorities regarding the colonization and degradation of PPE, as well as the release of toxic chemicals, were identified and discussed.