Objective To describe the epidemiology and clinical presentation of invasive non-typhoidal Salmonella (NTS) in Mozambique. Methodology We analysed the epidemiology, clinical presentation and serotype distribution of invasive NTS among Mozambican children admitted to the Manhiça District Hospital between May 2001 and April 2006. Results A total of 401 NTS cases were analysed; the median age was 16 months [interquartile range (IQR): 10-24]. Fever, cough and increased respiratory rate were the most common symptoms reported, while diarrhoea was present in only 29%. In the univariate analysis, invasive NTS was associated with age, fever, diarrhoea, increased respiratory rate, splenomegaly, hepatomegaly, severe malnutrition, and severe anaemia. Young age, severe malnutrition, diarrhoea and pneumonia were independent risk factors of death. S. typhimurium (66%), and S. enteritidis (25%) were the most frequent serotypes, with incidence rates of 240.4 and 108.6 per 100 000 child years among infants for S. typhimurium and S. enteritidis, respectively; and no significant differences were found regarding their clinical presentation. Resistance to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole was high for both S. typhimurium and S. enteritidis. Conclusions Clinical presentation of invasive NTS was non-specific and similar to that of other infections, with some factors being associated with NTS. Antibiotic resistance was very common to currently recommended and available antibiotics for suspected sepsis. © 2009 Blackwell Publishing Ltd.