Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. The development of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We tested vaccine candidates based on different target antigens that afforded protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A multivalent vaccine combining all tested antigens protected from morbidity at a very low dose of 50 ng per antigen after a single vaccination in mice. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.