The aim of this study was to evaluate the effects of synbiotic therapy in patients with short bowel syndrome (SBS). Four pediatric patients with SBS, who were receiving synbiotics therapy including Bifidobacterium breve, Lactobacillus casei and galactooligosaccharides, were enrolled in this study. We evaluated changes in immunonutritional parameters before and after receiving synbiotics therapy. Four normal, healthy, age-matched children were enrolled as controls. Fecal samples from patients and controls were collected and analyzed for fecal bacterial flora and organic acid (OA) contents. Levels of short chain fatty acids (SCFA) such as butyrate, propionate, and acetate increased in one patient, and SCFA/total OA levels increased in three patients. Serum lymphocyte counts and concentrations of pre-albumin increased after beginning synbiotics therapy, reaching a statistically significant level at the ninth month compared to the pre-treatment level. There was an increasing trend in height and weight gain velocity during the study compared with the pre-treatment period. The patients' fecal bacterial flora improved as a result of synbiotics therapy. Synbiotics therapy may be very effective at improving the intestinal flora and systemic immunonutritional status of patients with SBS.