Ovine mastitis is a significant production-limiting disease and the most important welfare problem of sheep, across all production types and all management systems. Control is based in a combination of management techniques, with little evidence available regarding applied immunoprotective measures. Objective of the experiment was to study the efficacy of a novel vaccine for protection of ewes against experimentally induced staphylococcal mastitis and to evaluate potential effects in milk yield of ewes. The vaccine induces antibodies against the poly-N-acetyl β-1,6 glucosamine exopolysaccharide, the main component of the extracellular biofilm matrix of staphylococci, and acts in preventing slime production and consequently biofilm formation by these organisms, which are a principal causal agent of ovine mastitis.