The aims of the present study were to: (i) analyze Acrp30 expression levels and its oligomerization state in a large cohort of CVID patients in maintenance Ig replacement therapy; (ii) determine whether Acrp30 fluctuations are related to different clinical phenotypes; (iii) investigate the role of Acrp30 in immunodeficiency by monitoring the levels of this adipokine in eight treatment-naïve CVID patients (i.e., patients not treated before diagnosis) before and after the first Ig replacement therapy administration versus. This evidence concerns the gene ADIPOQ and common variable immunodeficiency.