As a result of the selection for genotypes with greater sow prolificacy, litter size increased and, concomitantly, average litter birth weight and early postnatal survival rates of low birth weight (L-BtW) offspring decreased. This study compared the impact of l-carnitine (CAR) and l-arginine (ARG) supplemented with a milk replacer and fed to L-BtW piglets born from large litters from days 7 to 28 of age on growth performance, carcass composition, organ and Semitendinosus muscle (STM) development. A total of 30 female and castrated Swiss Large White piglets weaned at 7 days of age were assigned to three milk replacer diets containing either no supplement (CON), CAR (0.40 g/piglet per day) or ARG (1.08 g/kg BW per day). Piglets were kept in pairs in rescue decks (0.54 m2). They were weighed daily and daily allowance of both, feed and ARG, was adjusted accordingly. Thus, feed allowance depended on growth. Each day, the milk replacer was prepared with water (1:4). Feed (allowance: 60 g dry matter/kg BW per day) was offered daily in six equal rations. Feed intake and feed efficiency was assessed for the pairs and apparent total tract-energy and -protein digestibility was determined from days 21 to 28 of age. On day 28, piglets were euthanized, blood samples were collected and the whole STM and organs were weighed. In STM, the size and metabolic properties of myofibers were determined. No difference in growth performance was found between dietary treatments, but piglets from the CAR group tended (P<0.10) to grow faster during the 1st experimental week and consume more feed from days 14 to 21 as compared with piglets of the CON group. A setback in growth in the last week in the CAR group coincided with the lower (P<0.05) energy and protein digestibility. Dietary treatments had no effect on STM and organ weight and myofiber size. Compared with the other groups, there were trends (P<0.10) for blood serum urea and glucose level to be greater in CAR and for non-esterified fatty acid level to be greater in ARG piglets. The greater (P<0.05) ratio of lactate dehydrogenase to either citrate synthase or β-hydroxyacyl-CoA dehydrogenase indicated that the relative importance of the glycolytic compared with the oxidative pathway was greater in STM of CAR and ARG compared with CON piglets. These results suggest that ARG and CAR supplements were beneficial for muscle maturation whereas findings on phenotypic traits were rather unsystematic.