The authors systematically reviewed the literature on mannose-binding lectin (MBL) and infections in newborns to determine whether infection risk is increased in MBL-deficient newborns. All original reports on MBL and infections in newborns were retrieved from Embase, Medline and CENTRAL from 1966 to December 2009. Information extracted from each article included study design, definitions of MBL deficiency and neonatal infection, follow-up period and risk factor analysis. The validity of each study was assessed. Eight prospective cohort studies, including 3166 (range 47-1832) premature or term neonates, were assessed. MBL levels were measured in five studies and MBL2 genotype in six studies. Definitions of MBL deficiency and infection varied. In three out of five phenotypic studies low MBL levels were statistically significantly associated with increased culture-confirmed sepsis rates, also after correction for gestational age or birth weight. In the first study, the median MBL level was decreased in newborns with confirmed sepsis (170 μg/l) compared with newborns without sepsis (1450 μg/l). In two other studies, culture-confirmed sepsis was associated with MBL levels ≤700 μg/l (OR 15.0, 95% CI 1.5 to 151.3) and ≤400 μg/l (OR 3.1), respectively. The remaining two studies investigated various non-culture-confirmed infections. Only one study included the timepoint of clinical suspicion of infection in multivariate analysis. Contradicting results were reported in six MBL2 genotypic studies. Newborns with low MBL levels appear to have culture-confirmed sepsis more frequently than MBL-sufficient newborns. However, the influence of confounding factors was analysed insufficiently. Variant MBL2 genotypes appear to have less influence.