BACKGROUND Healthy, full-term, exclusively breastfed infants are expected to lose weight in the first days following birth. There are conflicting opinions about what constitutes a normal neonatal weight loss, and about when interventions such as supplemental feedings should be considered. OBJECTIVE To establish the reference weight loss for the first 2 weeks following birth by conducting a systematic review of studies reporting birth weights of exclusively breastfed neonates. METHODS We searched 5 electronic databases from June 2006 to June 2007: the Cochrane Database of Systematic Reviews; MEDLINE (from 1950); CINAHL (from 1982); EMBASE (from 1980); and Ovid HealthSTAR (from 1999). We included primary research studies with weight loss data for healthy, full-term, exclusively breastfed neonates in the first 2 weeks following birth. RESULTS Eleven studies met the inclusion criteria. Definitions, types of measurements, and reporting styles varied among studies. In most studies, daily weights were not measured and measurements did not continue for 2 weeks. Mean weight loss ranged from 5.7% to 6.6%, with standard deviations around 2%. Median percentage weight loss ranged from 3.2 to 8.3, with the majority around 6%. The majority of infants in these 11 studies regained their birth weight within the first 2 weeks postpartum. The second and third days following birth appear to be the days of maximum weight loss. DISCUSSION Methods used to report weight loss were inconsistent, using either an average of single lowest weights or a combination of weight losses. The 7% maximum allowable weight loss recommended in 4 clinical practice guidelines appears to be based on mean weight loss and does not account for standard deviation. Further research is needed to understand the causes of neonatal weight loss and its implications for morbidity and mortality.