Patients infected with the Omicron variant of SARS-CoV-2 mainly develop mild COVID-19, manifesting as upper respiratory symptoms, fatigue, and fever. Shufeng Jiedu capsule (SFJDC), a traditional Chinese medicine indicated for treatment of upper respiratory infections in China, was tested for its efficacy and safety in treatment of an Omicron infection at a mobile cabin hospital in response to an outbreak of COVID-19 in Shanghai, China in April 2022. In this open-label, randomized controlled trial, patients in the control group received best supportive care, while those in the test group received additional SFJDC therapy for 7 days. SFJDC markedly alleviated patients’ symptoms including a sore throat, coughing, fatigue, and a fever after 7 days of treatment. The virus negative time was significantly shorter in the SFJDC treatment group, but there were no obvious differences in the virus negative rate between the two groups at the end of the 7-day follow-up. These results suggest that patients with the Omicron infection may benefit from SFJDC treatment. Double-blind, randomized controlled trials are warranted to comprehensively evaluate the efficacy and safety of SFJDC in a large cohort study in the future.