Clostridioides difficile(C. difficile)and coronavirus disease 2019 (COVID-19) infections can have overlapping symptoms. Recently, the association and outcomes of coinfection have been studied. We present the case of an 83-year-old lady with Parkinson’s disease (PD) who was admitted with pneumonia secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. She was treated with empiric antibiotics ampicillin-sulbactam and azithromycin, along with antiviral therapy remdesivir and baricitinib, and dexamethasone. The patient developed severeC. difficileinfection with a leukemoid reaction. She was treated with intravenous metronidazole and oral vancomycin without any improvement. Before she could receive a fecal microbiota transplant, her infection progressed to fulminant colitis, and she required emergent surgery. The patient developed several complications post-surgery and succumbed to the severe illness. Our patient’s multiple comorbidities and an underlying COVID-19 infection predisposed her to severe illness. This case emphasizes the long-standing discussion on antibiotic stewardship and encourages a debate on the role of immunosuppressant antiviral medications and underlying PD in predisposing patients to a severeC. difficileinfection.