Pseudomonas aeruginosa is an opportunistic and highly virulent pathogen with an increasing prevalence of multi-drug resistant strains. In bacteraemia, P. aeruginosa is associated with significantly increased patient morbidity and mortality and poses a major risk for immunocompromised individuals and patients in intensive care units. The high incidence of intrinsic antibiotic resistance in P. aeruginosa and the rapidly growing number of extensively resistant strains necessitate the development of new treatments and drugs. Recently, a novel mechanism of serum resistance for P. aeruginosa was described which is mediated by the presence of ‘cloaking antibodies’ (cAb). In this mechanism, high titres of IgG or IgA specific for the O-antigen polysaccharide can actually prevent serum-mediated killing of P. aeruginosa. Although this phenomenon is well established in chronic P. aeruginosa lung infections, at present its role in acute bacteraemia is unknown. To investigate this, we collected 75 matched serum and bacterial blood isolates from patients with P. aeruginosa bacteraemia and screened for the presence of cAb. Strains were serotyped via PCR and the titre of antibody specific for their matched serotype O-antigen determined. Despite being an acute infection 46% of patient sera had significantly high antibody responses to their matched O-antigen serotype. To determine if this sera could inhibit serum-mediated killing of their P. aeruginosa, serum bactericidal assays were performed against their cognate strain (if sensitive to healthy control serum killing) or serotype-matched lab strains. Twenty-one of the 75 patient sera could inhibit healthy control serum killing of a P. aeruginosa strain, however as the majority of bacterial isolates were innately serum resistant, only four could inhibit their cognate strain. These results are the first to demonstrate the presence and clinical relevance of this cloaking mechanism in P. aeruginosa bacteraemia.