Abstract To raise piglets without antibiotics and high trace elements levels, favoring immune development and maturation is a potentially successful strategy, as long as over-stimulation of immune system does not harm animal performance. A trial was undertaken to evaluate response of piglet to varied blend of plant and yeast extracts selected for renowned effects on immune system. Weanling piglets (n = 400; 21 d of age), females and castrated males, were allocated to 4 dietary treatments across 80 pens: negative control (NC), blend of plant and yeast extracts for immune stimulation added to NC (B1), essential oils with anti-inflammatory properties added to B1 (B2), protected betaine added to B2 (B3). Pre-starter diets were fed from weaning to d 42, followed by starter diets offered until the end of the trial at d 69. On d 49, coughing and sneezing (CS) were counted per pen in both rooms, and individual fecal samples were taken from 20 piglets per diet, selected at weaning, to assay total peroxidase activity (TPO), a marker of gut inflammation. Statistical analyses were performed on pen data to analyze effects of treatment on piglet growth rate (average daily gain; ADG), feed intake (average daily feed intake; ADFI) and feed conversion ratio (FCR). The model included the effect of weaning weight, treatment, and interactions. Linear contrasts were used to compare B1 to NC, B2 to B1, and B3 to B2. A similar model was applied to individual fecal TPO measurements. Sneezing count frequency was analyzed with Chi² statistics and odd ratio (OR) were computed per treatment. Dietary treatment did not affect CS counts. Compared with NC, B1 reduced initial ADG and ADFI (from d 21 to 42) and increased initial FCR (P < 0.05). In the following period, ADG, ADFI and FCR improved with B1 (P < 0.05), resuming body weight (BW; final BW: 26.8, 26.8, 27.3 and 27.5, P > 0.20, for NC, B1, B2 and B3, respectively). Overall FCR slightly decreased (1.66 vs. 1.64, P < 0.05, for NC and B1 respectively). Compared with B1, B2 increased initial ADG and ADFI (ADG21-42: 0.244 vs. 0.258 kg, P < 0.05, for B1 and B2, respectively), and decreased FCR initial and overall (overall: 1,64 vs. 1.60, P < 0.05, for B1 and B2 respectively). B2 also minimized fecal TPO compared with other treatments (Uּּ•mL-1: 13.7 vs. 21.3 vs. 7.0 vs. 10.1, P < 0.001, for NC, B1, B2 and B3, respectively). B3 did not provide statistical benefit over B2. In this trial, immune stimulation decreased initial growth and reduced feed efficiency. Anti-inflammatory essential oils tempered consequences of gut inflammation and restored performance, while protected betaine did not provide additional benefit.