Blood group phenotypes have been associated with COVID-19 susceptibility and severity. This study aimed to examine ABO/Rh blood group distribution in COVID-19-related deaths considering demographics and pathological conditions. We conducted a retrospective study at the University Hospital Center Split, Croatia, that included 245 COVID-19 positive individuals that died from April 8, 2020, to January 25, 2021. We extracted data on their blood groups, demographics, and pre-existing comorbidities and compared findings with general population data from blood group donations (n = 101,357) and non-COVID-19 deaths from 2019 (n = 4968). The proportion of dead males was significantly higher than in non-COVID-19 cases (63.7% vs. 48.9%, P < 0.001), while the proportion of older individuals did not differ. The prevailing pre-existing diseases were hypertension (59.6%), diabetes (37.1%), heart failure (28.8%), digestive disorder (26.5%), and solid tumor (21.6%). The ABO distribution in the deceased and donors' group showed significant differences, with the higher prevalence of A/AB group and lower prevalence of 0, but with individual differences significant only for AB and non-AB groups. There was a reduced proportion of females within the deceased with group 0 (P = 0.014) and a higher proportion of AB individuals with coronary heart disease (P = 0.024). The study confirmed a higher risk of death in males. The lower proportion of type 0 in deceased individuals was greater in females, implying that group 0 is not necessarily an independent protective factor. Coronary heart disease was identified as a potential risk factor for AB individuals.