Monoclonal antibodies (mAbs) represent a highly beneficial tool for the prophylaxis and treatment of viral diseases, such as COVID-19 and influenza. MRNA lipid nanoparticle (LNP) technology, which can overcome limitations associated with recombinant mAb protein manufacture, has been demonstrated as a promising method for efficient mAb delivery. In this study, we contrasted mRNA/LNP versus recombinant proteins in delivering neutralising human mAbs against COVID-19 and influenza in mice. By modifying mRNA design, LNP formulation, and delivery route, we were able to modulate the efficiency, distribution, and durability of mAb expression in vivo. Notably, high mAb levels were achieved in both serum and mucosal compartments when a single mRNA encoding both heavy and light chains was delivered intravenously or intramuscularly using a prototypic LNP formulation analogous to the Pfizer COVID-19 vaccine. However, due to antibody responses to encoded mAbs, likely triggered by LNP components, mRNA-expressed mAbs rapidly declined after 7 days. Nevertheless, at early timepoints post injection, mRNA/LNP-delivered mAbs reached higher peak levels and conferred more effective protection against SARS-CoV-2 and influenza challenge compared to recombinant mAb proteins. Understanding the effects of platform composition and delivery strategies on the bioavailability of mAbs in vivo will provide guidance for the rational design of mRNA/LNPs for maximal protection against viral infection.