Increased circulating proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure (CHF). In vitro studies have suggested that vitamin D suppresses proinflammatory cytokines and increases anti-inflammatory cytokines. The aim of this work was to evaluate the effect of vitamin D supplementation on renin-angiotensin system cytokines as well as different clinical, biochemical, and echocardiographic variables in infants with chronic CHF. This was a double-blind, placebo-controlled intervention study and included 80 infants with CHF. The intervention consisted of either giving Vitamin D-3 oral drops (group I) or placebo oral drops (group II). In both study groups, baseline 25-hydroxyvitamin D [25(OH)D] concentrations were below the lower end of the reference range. After 12 weeks of intervention, vitamin D supplementation for group I infants caused significant improvement of HF score, left-ventricular (LV) end-diastolic diameter, LV end-systolic diameter, LV ejection fraction%, and myocardial performance index together with markedly increased serum 25(OH)D and interleukin (IL)-10 and decreased PTH, IL-6, and TNF-alpha compared with the placebo group; these differences were statistically significant (p < 0.001). Vitamin D supplementation has great benefits as an anti-inflammatory agent in infants with CHF. It helps acceleration of the clinical improvement and cytokine profile balance.