Aim: We aimed to investigate the role of adiponectin in acute rheumatic fever by evaluating correlations with cytokines and acute-phase reactants. Methods: Patients were divided into three groups by clinical findings. Group 1 included 8 patients with only chorea, Group 2 included 13 patients with arthritis and carditis, and Group 3 included 12 patients with only carditis. A total of 54 age- and gender-matched children were enrolled in the control group. Blood samples were drawn for analysing acute-phase reactants, adiponectin, tumour necrosis factor-alpha, interleukin-6, and interleukin-8 levels at baseline on Days 2, 5, 10, and 15, and at 8 weeks. Results: There was no statistically significant difference between baseline age, gender, body mass index, serum triglyceride, total cholesterol, and low-density lipoprotein levels of the study and control groups (p > 0.05). No correlation was found between baseline plasma adiponectin levels, age, body mass index, follicle-stimulating hormone, luteinising hormone, oestradiol, total testosterone, and blood lipid levels of the study and control groups (p > 0.05). We found that adiponectin and interleukin-6 levels increased, tumour necrosis factor-alpha levels decreased, and interleukin-8 levels remained unchanged in acute rheumatic fever, which is an inflammatory disease. Moreover, adiponectin level was higher and tumour necrosis factor-alpha level was lower in the improvement period in comparison with the acute period, particularly in the carditis group. Conclusion: It was considered that, increasing throughout the treatment period, adiponectin may have anti-inflammatory effects in acute rheumatic fever. In addition, adiponectin levels are associated with a decline in inflammatory mediators in rheumatic fever.