Non-pharmacological strategies that have been proposed by complementary medical systems, can be effective in management of COVID-19. This study was designed as a three-arm, assessor-blinded, randomized controlled trial. A total of 139 hospitalized COVID-19 patients were randomly assigned into three groups: (1) acupuncture (ACUG), (2) cupping (CUPG), and (3) control (CTRG). All participants received conventional treatment. The primary study endpoint included changes in respiratory signs including oxygen saturation (SpO 2) and respiratory rate (RR). The secondary endpoints were COVID-19-related hospitalization duration and serious adverse events such as intensive care unit (ICU) admission, intubation or death, all up to day 30. Also, improvements in cough, dyspnea, chest tightness, oxygen demand, anorexia, headache, weakness, sore throat, and myalgia were evaluated. Forty-two patients in ACUG, 44 patients in CUPG, and 42 patients in CTRG completed the trial. After 3 days, SpO 2 and RR improved significantly in CUPG and ACUG compared with CTRG (effect size 8.49 (6.4 to 10.57) and 8.51 (6.67 to 10.34), respectively: p < 0.001). Compared with CTRG, patients in CUPG and ACUG recovered faster (mean difference 6.58 (4.8 to 8.35) and 9.16 (7.16 to 11.15), respectively) and except for two patients in ACUG who were admitted to ICU, none of patients in ACUG or CUPG needed ICU or intubation (p < 0.001 in comparison to CTRG). Amelioration of clinical COVID-19 related symptoms reached a high level of statistical significance in CUPG and ACUG in comparison with CTRG (p < 0.01). Cupping and acupuncture are promising safe and effective therapies in management of COVID-19. TRIAL REGISTRATION: This study was registered at Iranian Registry of Clinical Trials IRCT20201127049504N1 (https://en.irct.ir/trial/52621).

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