Persons with trisomy 21 (Down syndrome) present different phenotypes, including early neurodegeneration, which is prominent in the brain olfactory areas, and olfactory deficit. The use of in vivo techniques in animal models allows to characterize and follow up these slowly developing phenomena. We explored by means of magnetic resonance imaging the olfactory bulb of the Ts65Dn mouse, an established model of Down syndrome, searching for possible syndrome‑related changes. In vivo imaging provided a first glimpse of the trisomic olfactory bulb as compared to euploid one. The olfactory bulb volume was smaller in trisomic mice, suggesting that changes in olfactory bulb may be apparent already in the young adult (2‑ to 8‑month‑old) mice, which are amenable to follow‑up in vivo. These findings lead the way to future work aimed at characterizing the Down syndrome‑related development of morphological alterations in the olfactory bulb and relating them to changes in olfactory performance, which were detected in this mouse model.