The complement activation product C5a may be an important mediator of tissue injury after decompression stress. This study investigated whether the administration of anti-C5a antibody may reduce changes after decompression in the lung and in the brain. Two groups of rabbits were used; one receiving anti-C5a monoclonal antibody (n = 7) and the other receiving a sham antibody as control (n = 7) before pressure exposure. Five rabbits (4 in the anti-C5a group and 1 in the control group) died during the 2-h observation period postdive due to massive bubbling. Polymorphonuclear leukocyte (PMN) infiltration of lung tissue and pulmonary edema was observed, but this accumulation was unaffected by anti-C5a pretreatment. However, a significant positive correlation was observed between PMN accumulation and survival time postdive. Brain-specific gravity was lower for the group treated with anti-C5a antibody compared to the control group. Further, it was lower for those rabbits that died early compared to the ones that survived the 2-h period. This study was unable to prove a protective effect on the blood-brain and blood-lung barrier by injecting anti-C5a antibody. A possible beneficial effect of anti-C5a antibody may be masked by the mechanical damage caused by the gas bubbles.