Litter size strongly affects reproductive output and is therefore of central interest for the understanding of life-history evolution. I investigated the effect of variation in litter size (natural and manipulated) on the energetics of reproduction in the highly precocial guinea pig (Cavia porcellus). Unlike the situation in altricial species, increasing litter size in this precocial rodent influenced maternal performance (increase in litter mass and decrease in mass of individual offspring) as strongly during gestation (68 days) as during lactation (20 days). To cover the energy cost of offspring production, mothers increased their daily food intake. Their daily increase in metabolizable energy intake varied significantly with litter size during gestation but not during lactation. Instead, offspring in large litters consumed more solid food during lactation than did offspring in small litters. The efficiency of energy conversion into offspring production was not affected by litter size, neither during gestation nor during lactation. Furthermore, manipulation of litter size did not influence a mother's total energy cost of lactation. As a consequence, offspring in enlarged litters grew significantly slower than offspring in reduced litters despite similar body masses at birth and significantly greater consumption of solid food by nursing offspring in large litters. Results suggest that the effect of litter size on the energetics of reproduction in the precocial guinea pig differs from that of altricial rodents. Consequently, ecological implications of variation in litter size in the precocial guinea pig might also be very different to those in altricial species.