Background: Probiotics are used as a means to improve animal health and intestinal development. Saccharomyces boulardii ( S. boulardii ) is a well-known probiotic, however, few studies have examined the effects of S. boulardii on weaned pig let performance. Therefore, this 28-day study compared the effects of S. boulardii mafic-1701 and aureomycin in weaned piglet diets on growth performance, antioxidant parameters, inflammation and intestinal microbiota. One hundred and eight weaned piglets were randomly divided into three dietary treatment groups: (1) basal diet (CON); (2) basal diet supplemented with 75 mg/kg aureomycin (ANT); (3) basal diet supplemented with 1 × 10 8 CFU/kg S. boulardii mafic-1701 (SB). Results: Compared to CON group, SB group had higher feed efficiency ( P < 0.01) and lower diarrhea rate ( P < 0.05) over the entire 28 days. Total superoxide dismutase concentration in serum was markedly increased in SB group ( P < 0.05). Moreover, compared with CON group, SB group decreased the level of pro-inflammatory cytokines interleukin-6 ( P < 0.01) and tumor necrosis factor ( P < 0.05) in jejunum. Supplementation with S. boulardii mafic-1701 increased abundance of Bacillus and Ruminococcaceae_UCG_009 ( P < 0.05), whereas abundance of unclassified _Clostridiaceae_4 was decreased ( P < 0.05). Furthermore, S. boulardii mafic-1701 administration increased cecal concentration of microbial metabolites , isobutyrate and valerate ( P < 0.05). Conclusions: The improvement in feed conversion ratio, reduction in diarrhea rate in weaned piglets provided diets supplemented with S. boulardii mafic-1701 may be associated with enhanced antioxidant activity, anti-inflammatory responses and improved intestinal microbial ecology.