The objective of this study was to investigate the effects of immunological challenge on the skeletal muscle fiber type conversion of piglets. Sixteen Large White weaned barrows (28 ± 3 d, 8.22 ± 0.89 kg BW) were allotted by weight and litter to 2 groups: the control group and the lipopolysaccharide (LPS) group. Saline (control) or LPS was injected intravenously via a jugular catheter on d 1, 3, 5, 7, 9, 11, 13, and 15 at an initial dosage of 80 μg/kg BW, which was increased by 30% at each subsequent injection. Blood samples were collected via the jugular catheter 3 h after the LPS challenge on d -1, 1, 5, 9, and 13. Muscle tissue samples were collected from the LM after exsanguination on d 15. The LPS challenge increased the plasma IL-6, tumor necrosis factor-α (TNF-α), cortisol, IL-1β, and haptoglobin concentrations on d 1 and 5 ( < 0.01) and increased the plasma IL-6 ( < 0.05), TNF-α ( < 0.05), and haptoglobin ( < 0.01) levels on d 9. Compared with that of the control group, the ADG of the LPS group decreased by 40.00% ( < 0.01), 29.52% ( < 0.05), and 19.30% ( < 0.05), and the ADFI decreased by 25.09% ( < 0.01), 23.15% ( < 0.05), and 19.47% ( < 0.05) during d 1 to 4, d 5 to 8, and d 9 to 15, respectively. In the LM of LPS-challenged piglets, myosin heavy chain 1 (MyHC1) mRNA and protein expression tended to be reduced ( = 0.08, 0.09), whereas mRNA, mRNA, and MyHC2 protein expression increased ( < 0.05). The LPS challenge reduced succinic dehydrogenase (SDH) activity ( < 0.05) and increased lactate dehydrogenase (LDH) activity ( < 0.05) in the LM of piglets. Compared with those in the control group, transcriptional peroxisome proliferator-activated receptor coactivator-α () mRNA ( < 0.05), calcineurin (CaN) mRNA, and protein expression were reduced ( < 0.05), and PGC-α protein expression tended to be reduced ( = 0.08) in the LM of LPS-challenged piglets. These results show that immunological challenge induced by LPS resulted in a shift from type I to type II fibers in the LM of piglets, which may be mediated by the downregulation of the CaN/PGC-α signaling pathway.