Hyper‐inflammation, cytokine storm, and recruitment of immune cells lead to uncontrollable endothelial cell damage in patients with coronavirus disease 2019 (COVID‐19). Sphingosine 1‐phosphate (S1P) signaling is needed for endothelial integrity and its decreased serum level is a predictor of clinical severity in COVID‐19. In this clinical trial, the effect of Fingolimod, an agonist of S1P, was evaluated on patients with COVID‐19. Forty patients with moderate to severe COVID‐19 were enrolled and divided into two groups including (1) the control group ( n = 21) receiving the national standard regimen for COVID‐19 patients and (2) the intervention group ( n = 19) that prescribed daily Fingolimod (0.5 mg) for 3 days besides receiving the standard national regimen for COVID‐19. The hospitalization period, re‐admission rate, intensive care unit (ICU) administration, need for mechanical ventilation, and mortality rate were assessed as primary outcomes in both groups. The results showed that re‐admission was significantly decreased in COVID‐19 patients who received Fingolimod compared to the controls ( p = .04). In addition, the hemoglobin levels of the COVID‐19 patients in the intervention group were increased compared to the controls ( p = .018). However, no significant differences were found regarding the intubation or mortality rate between the groups ( p > .05). Fingolimod could significantly reduce the re‐admission rate after hospitalization with COVID‐19. Fingolimod may not enhance patients' outcomes with moderate COVID‐19. It is necessary to examine these findings in a larger cohort of patients with severe to critical COVID‐19.