BACKGROUND: In this research study, we aimed to analyze the changes in the lymphocyte subsets in Saudi patients with Covid-19 and assess the possible association of differences in lymphocyte subsets with the infection in local population of Makkah city, Saudi Arabia. METHODS: Peripheral blood samples were collected from healthy and from Covid-19 patients admitted to Al Nour Hospital from October through December 2022. Flow cytometry (FCM) was used to measure the absolute and relative counts of lymphocyte subsets. RESULTS: The analysis showed that most patients with Covid-19 disease showed moderate illness. The observed symptoms were cough, fever, and feeling tired. In Covid-19 patients, a significant reduction in CD3+ T-cell, CD4+ T cell, CD8+ T cell, B cell, NK cell, and total lymphocyte cell counts have been seen when compared to the healthy control person. Also, the percentage of CD3+T-cells and CD4+ T-cells was significantly decreased in Covid-19 pa-tients compared to the control. In contrast, the percentage of CD4+CD8+ T-cells, CD16+CD56+ NK cells, and CD19+ B-cells was higher in Covid-19 patients versus the healthy control. CONCLUSIONS: Our results showed similar changes as in a previous meta-analysis study including the disease severity and lymphocyte subset counts in patients hospitalized with Covid-19 and could be used as prognostic strategy to predict the outcome and severity of Covid-19 disease. To better understand and explain this reduction, further analysis of other factors, such as IL-4, lymph tissues structure, and N protein-specific antibody, is needed.