Experimental studies have demonstrated the protective role of ectonucleotidases — particularly CD39 and CD73 — in limiting inflammation connected to a liver pathology. However, their expression in metabolic-associated fatty liver disease (MAFLD) has not been thoroughly investigated. This study aimed to evaluate the mRNA levels of the ENTPD1 and NT5E genes, which encode CD39 and CD73, respectively, in patients with different forms of MAFLD (liver steatosis (LS) and metabolic-associated steatohepatitis (MASH)), and to assess the expression of CD39- and CD73-positive cells following immune cell activation in vitro. The sample included 29 healthy donors and 56 MAFLD patients. We measured the mRNA levels of the ENTPD1 and NT5E genes, pro-inflammatory cytokines (IL-6, TNFα), fragmented cytokeratin-18, and the blood content of CD39⁺ cells. Another parameter measured in vitro was the effect of immune cell activation on the proportion of CD39⁺ and CD73⁺ cells in patients with MASH and healthy donors. The expression of the ENTPD1 gene (p = 0.007 vs. control group; p = 0.010 vs. LS group) and the proportion of CD39⁺ cells among monocytes (p = 0.004 vs. control group; p = 0.003 vs. LS group) and lymphocytes (p = 0.034 vs. control group) were lower in the MASH group compared with both the control and LS groups. Activation of cells from MASH patients increased the proportion of CD39⁺ lymphocytes, but not that of CD14⁺ monocytes. It also increased the proportion of CD73⁺ cells among both lymphocytes and CD14⁺ monocytes. Thus, further investigation into the roles of CD39 and CD73 in the context of MAFLD progression represents a promising avenue for future research.