Objective: The COVID-19 pandemic has posed significant global health challenges. Despite extensive research efforts, the inflammatory response triggered by SARS-CoV-2 remains to be further explored and understood. Our study aims to examine the changes in serum concentrations of pro-inflammatory adipokines-visfatin and leptin-in COVID-19 patients in relation to a healthy control group. Patients/Materials/Subjects and Methods: The study consisted of forty COVID-19 patients and twenty-four healthy patients in the control group. Two serum samples were collected: upon admission and on the seventh day of hospitalization. Concentrations of visfatin and leptin in the serum, alongside routine biochemical parameters, were measured using enzyme immunoassay or enzyme-linked immunosorbent assay kits. The Shapiro-Wilk test was used to assess normality. Differences between independent groups were compared using the Mann-Whitney U test and Kruskal-Wallis ANOVA. Correlations were evaluated with Spearman's rank correlation coefficient. Results: Our findings revealed significantly lower visfatin levels in COVID-19 patients compared to the control group upon admission (4.29 ng/mL, (3.0-6.88 ng/mL) vs. 37.16 ng/mL (24.74-50.12 ng/mL), p < 0.001 for visfatin 1 and 52.05 ng/mL, (31.2-69.66 ng/mL) vs. 37.16 ng/mL (24.74-50.12 ng/mL), p = 0.048 for visfatin 2). The visfatin level of COVID-19 patients returned to the normal levels, established in the control group. However, there was no significant difference in leptin levels between the two groups (p = 0.270 for leptin 1 and p = 0.129 for leptin 2). There was a positive correlation between BMI and leptin concentration (r = 0.66 and p = 0.00). Moreover, it was discovered that COVID-19 independently reduces visfatin levels during the first day of illness. Conclusions: The results of our research suggest that the onset of COVID-19 infection is correlated to visfatin levels. Association with leptin levels remains inconclusive. Further research is imperative to elucidate the intricate role of visfatin and leptin in SARS-CoV-2 infection and their potential as biomarkers for COVID-19 severity and prognosis.