AbstractCOVID-19 has impacted populations across the globe and has been a major cause of morbidity and mortality. Influenza is another potentially deadly respiratory infection that affects people worldwide. While both of these infections pose major health threats, little is currently understood regarding the clinical aspects of influenza and COVID-19 co-infection. Our objective was to therefore provide a systematic review of the clinical characteristics, treatments, and outcomes for patients who are co-infected with influenza and COVID-19. Our review, which was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, involved searching for literature in seven different databases. Studies were eligible for inclusion if they included at least one co-infected patient, were available in English, and described clinical characteristics for the patients. Data were pooled after extraction. Study quality was assessed using the Joanna Brigg’s Institute Checklists. Searches produced a total of 5096 studies, and of those, 64 were eligible for inclusion. A total of 6086 co-infected patients were included, 54.1% of whom were male; the mean age of patients was 55.9 years (SD = 12.3). 73.6% of cases were of influenza A and 25.1% were influenza B. 15.7% of co-infected patients had a poor outcome (death/deterioration). The most common symptoms were fever, cough, and dyspnea, with the most frequent complications being pneumonia, linear atelectasis, and acute respiratory distress syndrome. Oseltamivir, supplemental oxygen, arbidol, and vasopressors were the most common treatments provided to patients. Having comorbidities, and being unvaccinated for influenza, were shown to be important risk factors. Co-infected patients show symptoms that are similar to those who are infected with COVID-19 or influenza only. However, co-infected patients have been shown to be at an elevated risk for poor outcomes compared to mono-infected COVID-19 patients. Screening for influenza in high-risk COVID-19 patients is recommended. There is also a clear need to improve patient outcomes with more effective treatment regimens, better testing, and higher rates of vaccination.