Background: Hypernatremic dehydration (HD) is a situation of high morbimortality in infants, and a crescent number of cases in exclusively breastfed infants has been reported. Research aim: To describe a cohort of exclusively breastfed infants with excessive weight loss (EWL) and/or HD, born at a Baby-Friendly certified Hospital in Portugal, serving a population with high rate of African immigrants. Methods: We performed a retrospective study of exclusively breastfed infants with EWL/HD and no less than 37 weeks of gestational age (GA), delivered between 2013 and 2015. Results: A cohort of 329 infants with EWL/HD was identified, corresponding to 5% of the total of newborns in the studied period. 65.3% of mothers were primiparous; average maternal age was 30 years. 51.7% of infants had a cesarean delivery. The average birth weight was 3,280 grams and the median GA was 39 weeks; 81.5% began breastfeeding within one hour of life. The diagnosis of EWL/HD was made at the Obstetric Nursery in 98.2% of cases, and of these 10.8% were admitted into the Neonatal Intensive Care Unit (NICU). The most commonly associated signs and symptoms were jaundice (64.1%) and hypoglycemia (15.2%); serious neurological complications were rare (0.6%) (seizures in one case and intraventricular hemorrhage in another). The average weight loss was 11.1% and 10.6%, respectively in cesarean and vaginal delivery infants (p = 0.02). In 76.1% infants, EWL was diagnosed in the first 72 hours of life; 44.7% had hypernatremia. The most common treatment was supplementation with infant formula (68.1%). Conclusions: EWL/HD were common among the studied population, namely in neonates born to primiparous mothers and by cesarean. Complications were rare and treatment mainly noninvasive. It seems fair to conclude EWL/HD are potentially serious problems, but with simple, inexpensive solutions when diagnosed early.