Pharmacological CNP administration improved microvascular perfusion, cardiac output, and inflammation in wild-type and ecCNP<sup>-/-</sup>, but not NPR-C<sup>-/-</sup>, mice.<h4>Conclusions</h4>Endogenous CNP plays a protective role in sepsis by preserving microvascular perfusion, reducing inflammation, maintaining endothelial integrity, and sustaining cardiac function via NPR-C. Here, NPR3 is linked to Sepsis.