Introduction: COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 increasingly involves people worldwide. Probiotics can improve immune system functions via different mechanisms. We proposed that Synbiotic Lactocare® may also reduce SARS-Cov2 infection in high risk medical staff working in COVID-19 hospital wards. Method: In a randomized, controlled trial, 60 hospital staff without any history of clinical or laboratory evidence of SARS-Cov2 infection were received either once daily oral synbiotic capsule (Lactocare®) that contains 1 billion CFU/Cap of L. (Lactobacillus) casei, L. rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, L. acidophilus, Bifidobacterium infantis, L. bulgaricus, and Fructooligosacharide (Zist Takhmir, Tehran, Iran) or placebo with the same appearance for 30 days. They were followed for two months. Result: During the two month period of this study, SARS-COV-2 RT-PCR test results were positive in three participants (9.67%) in placebo group compared to zero positive test in synbiotic group. The differences were not statistically significant (p= 0.238). During the study, two persons (7 %) of placebo group had respiratory complaint such as cough, rhinorrhea and/or dyspnea, compared with one in synbiotic group (p= 0.492). Conclusion: This study showed that overall frequency of SARS-COC2 infection in participants receiving synbiotic and those receiving placebo did not differ significantly. However, 3 hospital staff in placebo group compared to no one in synbiotic group had SARS-COV2 infection. Further studies with greater power and alternative probiotic strains and mixture are warranted to determine whether Synbiotic can prevent COVID-19 in at-risk hospital staff. Keywords: COVID-19, Synbiotic, prevention, Lactocare, SARS-Cov2