Some studies have found that unilateral cerebral damage produces significant deficits in the ipsilesional, "less-affected", body side. Other studies have found that such damage results in a paradoxical hyperfunctionality of the ipsilesional body side and a facilitation of learning-induced neuroplastic changes in the contralesional motor cortex. The purpose of this study was to determine whether these effects co-exist and/or vary with lesion severity. After small or large unilateral ischemic lesions of the sensorimotor cortex (SMC) or sham operations, adult male rats were trained for 20 days to acquire a motor task, skilled reaching for food, for the first time with the ipsilesional forelimb. Analyses of movement patterns indicated lesion-size-dependent ipsilesional abnormalities in grasping, retrieving and releasing food pellets. Despite these impairments, success rates were significantly increased and aiming errors reduced in lesion groups compared with sham operates. Performance was best in rats with small lesions that had more minor ipsilesional impairments. In the motor cortex contralateral to the lesion and trained limb, there were significant increases in the density of dendrites immunoreactive for microtubule-associated protein-2 (MAP2) and of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) immunoreactivity compared with sham operates. These effects were correlated with reaching performance. Therefore, enhanced motor skill learning in the "less-affected" forelimb and contralesional neuroplastic changes are muted after larger lesions and co-exist with ipsilesional impairments. These effects may be related to a denervation-induced neural restructuring of the contralesional cortex that both disrupts pre-existing motor engrams and facilitates the establishment of new ones.