Acutely ill children (n = 129) aged 1-6 years receiving antibiotic therapy were randomized to receive a nutritional supplement with (PS) or without (P) synbiotics or a fruit-flavored drink (D) with their medications. Group PS had significantly greater weight gains (versus D) following antibiotic therapy. The percentages of subjects without bacterial illnesses 14 days following antibiotic therapy were as follows: 94.3% (PS), 87.8% (D), and 80.6% (P). PS (vs D) significantly increased fecal Lactobacillus in a subset of subjects. Oral supplements increase energy intake and promote weight gain in acutely ill children receiving antibiotics; synbiotics may confer additional benefits by increasing bifidobacteria levels.