Probiotics (PRO) modulate immunity in humans, while the effect of prebiotics (PRE) and synbiotics (SYN) on the human immune system are not well studied yet. The objective of this study was to investigate whether daily intake of a SYN modulates immune functions. In a randomised double-blind, placebo-controlled trial, thirty-four colon cancer patients who had undergone ‘curative resection’ and forty polypectomised patients participated. Subjects of the SYN group daily received encapsulated bacteria (1 × 1010 colony-forming units of Lactobacillus rhamnosus GG (LGG) and 1 × 1010 colony-forming units of Bifidobacterium lactis Bb12 (Bb12)) and 10 g of inulin enriched with oligofructose. Controls received encapsulated maltodextrin and 10 g of maltodextrin. Prior to intervention (T1), and 6 (T2) and 12 weeks after the start of the intervention (T3), phagocytic and respiratory burst activity of neutrophils and monocytes, lytic activity of natural killer cells and production of interleukin (IL)-2, IL-10 and IL-12, as well as tumour necrosis factor-α and interferon-γ (IFN-γ) by activated peripheral blood mononuclear cells (PBMC) were measured. In faeces, the concentrations of transforming growth factor-β1 and prostaglandin E2 were measured. IL-2 secretion by activated PBMC from the polyp group increased significantly between T1 or T2 and T3 (P < 0·05). In the cancer group, SYN treatment resulted in an increased capacity of PBMC to produce IFN-γ at T3 (P < 0·05). Other immunity-related parameters were not affected by SYN treatment, neither in the cancer nor in the polyp group. In conclusion, supplementation with this SYN has minor stimulatory effects on the systemic immune system of the two study groups. Further studies in humans should aim to focus on the gut-associated immune system.