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No effective treatments can ameliorate symptoms of long COVID patients. Our study assessed the safety and efficacy of human umbilical cord‐derived mesenchymal stem cells (UC‐MSCs) in the treatment of long COVID patients. Ten long COVID patients were enrolled and received intravenous infusions of UC‐MSCs on Days 0, 7, and 14. Adverse events and clinical symptoms were recorded, and chest‐high‐resolution CT (HRCT) images and laboratory parameters were analyzed. During UC‐MSCs treatment and follow‐up, we did not observe serious adverse events, the symptoms of long COVID patients were significantly relieved in a short time, especially sleep difficulty, depression or anxiety, memory issues, and so forth, and the lung lesions were also repaired. The routine laboratory parameters did not exhibit any significant abnormalities following UC‐MSCs transplantation (UMSCT). The proportion of regulatory T cells gradually increased, but it was not statistically significant until 12 months. The proportion of naive B cells was elevated, while memory B cells, class‐switched B‐cells, and nonswitched B‐cells decreased at 1 month after infusion. Additionally, we observed a transient elevation in circulating interleukin (IL)−6 after UMSCT, while tumor necrosis factor (TNF)‐α, IL‐17A, and IL‐10 showed no significant changes. The levels of circulating immunoglobulin (Ig) M increased significantly at month 2, while IgA increased significantly at month 6. Furthermore, the SARS‐CoV‐2 IgG levels remained consistently high in all patients at Month 6, and there was no significant decrease during the subsequent 12‐month follow‐up. UMSCT was safe and tolerable in long COVID patients. It showed potential in alleviating long COVID symptoms and improving interstitial lung lesions. [ABSTRACT FROM AUTHOR]