These data demonstrate that: (i) CoV-2 infection alters ACE2 levels and viral loads differently in male and female mice; (ii) SARS-CoV-2 infects and persists in adipose tissue; (iii) adipose tissue in females may act as a sink/reservoir for CoV-2; and (iv) an inverse relationship exists between the viral loads in the lungs and adipose tissue. Here, ACE2 is linked to COVID-19.