In CO-poisoned patients without loss of consciousness no significant long-term functional differences in outcome have been shown in any hyperbaric versus normobaric oxygen studies. Since brain histology changes cannot be studied in CO-poisoned patients we evaluated the efficacy of normobaric and hyperbaric oxygen therapy in preventing brain cell injury in CO-poisoned animals without loss of consciousness. Wistar rats without loss of consciousness after exposure to 3000ppm of CO for 60min were exposed to ambient air (group 1), 100% oxygen at a pressure of 1bar (group 2) and 100% oxygen at a pressure of 3bar (group 3). The rats were sacrificed after two weeks, brain samples were stained with hematoxylin-eosin and a percentage of pyknotic cells in hippocampus was reported. Analyses of differences in percentage of pyknotic cells between different kinds of therapy showed that the percentage of pyknotic cells of the second group (2.3+/-1.2%) treated with normobaric oxygen and the third group (4.5+/-4.0%) treated with hyperbaric oxygen were similar, and both of them were significantly different, with a much lower percentage of pyknotic cells, from the first group left on ambient air (47.7+/-10.0%). In conclusion, immediate normobaric and hyperbaric oxygen therapy equally prevents hippocampal cell injury in CO-poisoned rats without loss of consciousness.