Childhood respiratory tract infections (RTIs) pose a significant health burden, especially in children under six years old. The main objective of this systematic review was to assess the effectiveness of vitamin D supplementation in the prevention of RTI in this population while also exploring potential effect modifiers such as age, baseline vitamin D status, and type of respiratory infection. A systematic review of the literature published up to February 2023 was conducted according to PRISMA guidelines, searching PubMed, Web of Science, Cochrane, and Scopus databases. Eight studies met the inclusion criteria, which investigated the association between vitamin D supplementation and respiratory infections in children between zero and five years old. The included studies were conducted between 2012 and 2021, encompassing a total of 2189 children from five randomized trials, two case-control studies, and one prospective cohort study. The relationship between vitamin D supplementation and the prevention of childhood RTI was not consistently observed across all included studies. Pooled results demonstrated varied effects of vitamin D supplementation on respiratory infection incidence, severity, and symptoms. Three studies reported statistically significant associations between low vitamin D levels and respiratory infections (OR = 4.90, OR = 6.97), while one study found that children who received vitamin D supplementation of 800 UI/day for 3 months during the cold season had fewer episodes of respiratory symptoms (RR = 0.55) and recovered more quickly from acute RTI. Lastly, according to one study, vitamin D intake < 80 IU/kg/day was significantly associated with the risk of acquiring pneumonia (OR 7.9) but not bronchiolitis. The remaining five studies found no statistically significant differences in infection rates or severity (p-value > 0.050). The available evidence on the effectiveness of vitamin D supplementation for preventing and treating respiratory infections in children under six years old is limited, with only a few favorable effects being reported. In some cases, a dose of 80 UI/kg/day was found to provide significant protection for acute respiratory infections, although in the major trials the only benefit was a quicker recovery and fewer respiratory symptoms, with no impact on incidence and severity of respiratory infections. Nevertheless, the study protocol, the supplementation dose, and duration of supplementation had significant variations between studies, leading to inconclusive findings.