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-α 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.