weaning. Rev. Vet. 32: 2, 230-233, 2021. Weaning is considered the most stressful period in pig production and is associated with intestinal and muscular disorders and poor productive performance. Studies show that creatine supplementation favors protein synthesis. The objective of this research was to evaluate the effect of creatine supplementation in piglets by measuring productive performance and biochemical tests in blood. The research was carried out at the Uyumbicho Experimental Center (UEC) belonging to the Faculty of Veterinary Medicine and Zootechnics of the Central University of Ecuador. A total of 16 piglets (Landrace x Yorkshire x Pietrain x Duroc) were used. The piglets were randomly distributed in each of the 4 treatments: T1 = control 1 (without milk supplement), T2 = control 2 (milk supplement), T3 = milk supplement + creatine (0.5%), T4 = milk supplement + creatine (1%). Piglets that received 1% creatine had the highest daily feed intake (0.432 kg/day) and the highest daily weight gain (0.336 kg/day) (42 days old) and the best feed conversion rate (1.288 kg/kg) (62 days old). The creatine kinase enzyme presented the highest value (2007.5 UL) in the piglets of control group 1. The use of a milk substitute and creatine supplementation mitigates the adverse effects post-weaning in piglets.