In clinical and military procedures, hyperbaric hyperoxia can lead to CNS oxygen toxicity (seizures) via CO₂-chemoreceptors stimulation and hyperventilation. This phenomenon is currently unpredictable. Using RT, we tested if seizures are preceded by a conventional pattern of hyperoxic hyperventilatory response (HBO₂VR), if the oxidative preconditioning (HBO₂PC) extends latency to seizure (LS) and if HBO₂VR and hypercapnic ventilatory response (HCO₂VR) are correlated. 87 male rats were implanted with RT modules to record EEG, diaphragmatic electromyogram (dEMG), & ECG. Rats were dived 3 times to seizures, once/week at 4, 5 or 6 ATA O₂ and subsequently to one HBO₂PC treatment 24 hours prior to repeating the dive series. Later, rats were exposed 3 times to a 2nd HBO₂ level. Our results showed that: a) LS for rats that never experienced seizures before was longer than LS for pre-exposed animals (+/­SD,min): 4ATA LS=96.1+/­10.2 vs 25.3+/­2.8; and 5ATA LS=29.2+/­4.4 vs 13.0+/­1.7; b) at 6ATA LS=4.8+/­0.6; c) in all dives HBO₂ caused a significant increase in dEMG that peaked <2–8min before seizures; d) HBO₂VR decreased after HBO₂PC; e) there is a positive correlation between HCO₂VR and HBO₂VR at 4ATA (r²=0.84) and 5ATA (r²=0.65). In summary, during HBO₂, neural plasticity affects LS and respiration patterns ([uarr] dEMG before seizures) both modulated by HBO₂PC and history effect on seizures. Also, the correlation between HCO₂VR and HBO₂VR suggests a co-activation of CO₂-chemoreceptors.