The objective of this study was to evaluate the effects of dietary nucleotide supplementation on growth performance, serum immunoglobulin G (IgG) and uric acid levels, immune-related organs, and intestinal morphometric parameters of broiler chickens under pre- and post-inflammatory challenge with lipopolysaccharide (LPS). Ninety-six seven-day-old male broiler chicks were randomized in a 2×2 factorial design composed of two dietary types (supplemented with 0 and 0.3 g of purified nucleotides/kg of feed) and two inflammatory conditions (with and without LPS administration) with eight replicates per treatment and three birds per cage. The experimental period was divided into two phases: 7-20 days of age (pre-LPS challenge) and 21-35 days of age (post-LPS challenge). Data were analyzed using one-way and two-way ANOVA for the pre- and post-challenge phases, respectively. During the prechallenge phase, dietary nucleotide supplementation improved body weight (982 vs. 1009 g/bird), daily weight gain (58.1 vs. 60.1 g/bird), feed conversion rate (1.28 vs. 1.25 g/g), and serum concentration of IgG (1.17 vs. 1.76 mg/mL) of broilers. During the post-challenge phase, nucleotide supplementation increased serum IgG of broilers at 28 days of age (3.01 vs. 4.34 mg/mL). For the intestinal morphometric parameters, nucleotide supplementation increased villus height (299.3 vs. 315.6 μm). Dietary nucleotide supplementation improves the performance of broilers from seven to 20 days of age (pre-LPS challenge). However, from 21 to 35 days of age, supplementation of 0.3 g of purified nucleotides/kg of feed, independent of inflammatory challenge, does not contribute to improve performance of broilers. Additionally, nucleotide supplementation increases IgG production and villus height in the jejunum of broilers