Epidemiological and clinical studies suggest that early-life stress (ELS) may lead to the development of mental disorders in adulthood. Maternal separation (MS) is a valid animal model of ELS that produces detrimental effects on brain and behavior of experimental animals. Positive environmental stimuli have been shown to counteract the behavioral deficits of ELS and enhance neuroplasticity. Recent data indicate that music may serve as a form of environmental enrichment in experimental animals. However, the underlying mechanisms through which musical enrichment exerts its effects are poorly understood. Male Sprague-Dawley rats were submitted to a 3 h MS protocol during postnatal days (PND) 2-14, while another group was left undisturbed. Half of the animals within each group were exposed from PND 21 to PND 76 for 12 h/day to Mozart K. 448. At approximately three months of age, elevated plus maze procedure, forced swim test and social approach task were applied to test whether music exposure can mitigate the effects of MS stress on animal emotional behaviors. Moreover, we investigated the effects of these treatments on dendritic spine density in the CA1 region of hippocampus. As expected, MS rats showed decreased sociability, increased anxiety- and depressive-like behaviors, and decreased mature dendritic spines in the CA1 region of hippocampus in adulthood. Musical enrichment reversed these effects. Our results suggest that musical enrichment can reverse the negative effects of MS on anxiety, depression, and sociability in adult rats and modulate neuronal plasticity and provide additional data for a new therapeutic intervention to rescue emotional symptoms.