We examined the longitudinal hypothalamic morphology in the progression of mild cognitive impairment (MCI). We used multivariable linear modelling to differentiate the structural volumetric change in the hypothalamic nuclei in nine females who developed MCI after 5 years and 61 healthy controls. We found significantly decreased left anterior-inferior (p<0.01), left anterior-superior (p<0.05), and left posterior (p<0.01) hypothalamic regions among females with MCI compared to healthy controls. There was also a significant asymmetry at the anterior-superior hypothalamus (p<0.05) in MCI females than in healthy controls. Thus, the degradation of the specific left hypothalamic subregions and leftward lateralization over time highlight the impact of early- stage MCI on the morphology of hypothalamus.