This study was designed to investigate the effects of multi-enzyme on diarrhea and immune responses of weaned pigs. A total 36 weaned pigs (5.92 ± 0.48 kg BW; 28 d old) were randomly allotted to 2 dietary treatments (3 pigs/pen, 6 replicates/ treatment) in a randomized complete block design. The dietary treatments were a typical diet based on corn and soybean meal (CON) and CON with 0.1% multienzyme (Multi; mixture of β-mannanase, xylanase, α-amylase, protease, β-glucanase, and pectinase). Pigs were fed their respective diets for 6 wk. Frequency of diarrhea, levels of packed cell volume (PCV), white blood cells (WBC), immunoglobulins, cortisol, tumor necrosis factor-α (TNF-α), transforming growth factor- β (TGF-β), and C-reactive protein (CRP) were measured. Multi group tended to decrease (p<0.1) diarrhea frequency than CON group during 2 wk after weaning. Lower values of PCV on d 3 (p<0.05) and d 7 (p<0.1) were found in Multi group compared with CON group. There were no significant differences on WBC number and immunoglobulin (Ig) M and A between Multi and CON groups. However, Multi group tended to increase (p<0.1) Ig G on d 7 than CON group. Moreover, Multi group showed modulated immune responses, indicated by decreased levels of cortisol (p<0.05) on d 7 and 14, TNF-α on d 3 (p<0.05) and d 7 (p<0.10), TGF- β on d 2 (p<0.05) and d 7 (p<0.10), and CRP (p<0.10) on d 3 and 7 after weaning compared with CON group. Consequently, inclusion of multi-enzyme in diets for weaned pigs improved gut health and modulated immune responses of weaned pigs.