An experiment was conducted to evaluate the effects of inclusion of Catfish (Pangasius hypophthalmus) by-product protein hydrolysate (CPH) and β-glucan produced from brewer’s yeast cell (BG) in diets on the performance and health status of weaned piglets. A total of 48 crossbred castrated (Yorkshire x Landrace) male piglets (8.0 ± 1.5 kg/piglet) at weaning were allocated to four treatment groups in a randomized complete block design. In each group, the piglets were divided randomly into 4 pens (replicates) with 3 piglets per pen. The control diet contained marine fishmeal (FM) as the sole protein supplement (FMD), and the experimental diets consisted of three different diets, in which 100% crude protein (CP) from FM in the FMD was replaced by the CP from CPH (CPHD) without any β-glucan product, and with commercial β-glucan (CPHCB) or β-glucan produced from brewer’s yeast cell (CPHBG) at 0.1%. Average daily gain (ADG) was highest in CPHBG; the lowest was in FMD. Feed consumption was lowest in CPHD and highest in FMD. Feed conversion ratio (FCR) was poorest in FMD and similar in the other three diets. Piglets fed diets with β-glucan from brewer’s yeast cell product and commercial β-glucan were less affected by diarrhoea and had less E.coli in feces than piglets fed the FMD diet. The cost/gain was lowest in piglets fed CPHBG and highest in FMD. In conclusion, it was best to combine the catfish by-product protein hydrolysate and β-glucan from brewer’s yeast cell in diets for weaned piglets, resulting in improved average daily gain and feed conversion ratio, and reduced diarrhoea incidence, fecal score and E.coli in feces.