SummaryDespite significant global morbidity associated with respiratory infection, there is a paucity of data examining the association between severity of non‐SARS‐CoV‐2 respiratory infection and blood group. We analysed a prospective cohort of adults hospitalised in Bristol, UK, from 1 August 2020 to 31 July 2022, including patients with acute respiratory infection (pneumonia [n = 1934] and non‐pneumonic lower respiratory tract infection [NP‐LRTI] [n = 1184]), a negative SARS‐CoV‐2 test and known blood group status. The likelihood of cardiovascular complication, survival and hospital admission length was assessed using regression models with group O and RhD‐negative status as reference groups. Group A and RhD‐positive were over‐represented in both pneumonia and NP‐LRTI compared to a first‐time donor population (p < 0.05 in all); contrastingly, group O was under‐represented. ABO group did not influence cardiovascular complication risk; however, RhD‐positive patients with pneumonia had a reduced odds ratio (OR) for cardiovascular complications (OR = 0.77 [95% CI = 0.59–0.98]). Compared to group O, group A individuals with NP‐LRTI were more likely to be discharged within 60 days (hazard ratio [HR] = 1.17 [95% CI = 1.03–1.33]), while group B with pneumonia was less likely (HR = 0.8 [95% CI = 0.66–0.96]). This analysis provides some evidence that blood group status may influence clinical outcome following respiratory infection, with group A having increased risk of hospitalisation and RhD‐positive patients having reduced cardiovascular complications.