Iron is a fundamental nutrient for human and microbial life. We sought to examine the association of iron deficiency versus normal iron status with the susceptibility to infections. A systematic search in the PubMed and Scopus databases was performed to identify relevant clinical studies. Six studies (including a total of 1,422 participants) met the inclusion criteria: four prospective cohort (859 participants), one retrospective case-control (115 participants), and one retrospective cohort study (448 participants). Intensive care unit (ICU)-acquired and postoperative infections were more common in patients with iron deficiency than among those with normal iron status in two studies, while no difference was reported in another study. In one study examining pregnant women with normal mean iron values, higher soluble transferrin receptor values independently predicted vaginosis-like microflora. Iron deficiency anemia was an independent predictor of respiratory tract infections in one study, and postoperative urinary tract infections were more common in patients with iron deficiency anemia in another. The limited available evidence suggests that individuals with iron deficiency and those with iron deficiency anemia may be more susceptible to infections than patients with normal iron status. Future studies should elucidate further these findings.