BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that was first discovered in December 2019 in Wuhan, China. With the growing numbers of community spread cases worldwide, the World Health Organization (WHO) declared the COVID-19 outbreak as a pandemic on March 11, 2020. Like influenza viruses, SARS-CoV-2 is thought to be mainly transmitted by droplets and direct contact, and COVID-19 has a similar disease presentation to influenza. Here we present a case of influenza A and COVID-19 co-infection in a 60-year-old man with end-stage renal disease (ESRD) on hemodialysis. CASE PRESENTATION: A 60-year-old man with ESRD on hemodialysis presented for worsening cough, shortness of breath, and diarrhea. The patient first developed a mild fever (37.8 °C) during hemodialysis 3 days prior to presentation and has been experiencing worsening flu-like symptoms, including fever of up to 38.6 °C, non-productive cough, generalized abdominal pain, nausea, vomiting, and liquid green diarrhea. He lives alone at home with no known sick contacts and denies any recent travel or visits to healthcare facilities other than the local dialysis center. Rapid flu test was positive for influenza A. Procalcitonin was elevated at 5.21 ng/mL with a normal white blood cell (WBC) count. Computed tomography (CT) chest demonstrated multifocal areas of consolidation and extensive mediastinal and hilar adenopathy concerning for pneumonia. He was admitted to the biocontainment unit of Nebraska Medicine for concerns of possible COVID-19 and was started on oseltamivir for influenza and vancomycin/cefepime for the probable bacterial cause of his pneumonia and diarrhea. Gastrointestinal (GI) pathogen panel and Clostridioides difficile toxin assay were negative. On the second day of admission, initial nasopharyngeal swab came back positive for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The patient received supportive care and resumed bedside hemodialysis in strict isolation, and eventually fully recovered from COVID-19. CONCLUSIONS: We presented a case of co-infection of influenza and SARS-CoV-2 in a hemodialysis patient. The possibility of SARS-CoV-2 co-infection should not be overlooked even when other viruses including influenza can explain the clinical symptoms, especially in high-risk patients.