Organophosphate (OP) poisoning is a serious global health concern responsible for more than three million poisonings worldwide each year. OP-induced respiratory failure is associated with an unacceptably high mortality rate. Caffeine has been successfully used in other cases of central respiratory failure. We hypothesized that caffeine administration would mitigate respiratory failure in an animal model of OP poisoning. We used a previously validated animal model of OP-induced central apnea with detailed physiologic respiratory recordings. The model consisted of Wistar rats that were anesthetized but spontaneously breathing 100% oxygen. Airflow, respiratory rate, tidal volume, mean arterial pressure and pulse rate were digitally recorded for 120 min following OP exposure or until death. The two study groups included dichlorvos and saline (n = 8) or dichlorvos and caffeine (n = 8). In all groups, dichlorvos was given as a single subcutaneous dose of 100 mg/kg (3x rat LD50). In each group caffeine (20 mg/kg) or saline (same volume) was given as a single intravenous (IV) injection 1 min prior to exposure to dichlorvos. Primary outcome was time to apnea. Data are presented as mean (stdev). Comparison between groups was performed using Student’s t Test and analysis of variation (ANOVA). There was no difference between group respiratory parameters during the baseline period. There was no difference in mortality between the groups (100% both) but the time to apnea differed significantly (p < 0.001). Animals pre-treated with caffeine demonstrated apnea 30.6 (8.7) min post dichlorvos exposure. Animals pre-treated with saline demonstrated apnea 12.2 (3.9) min post exposure. The rate of decline in respiratory rate and tidal volume was less in animals pre-treated with caffeine. In conclusion, in a rat model of dichlorvos poisoning with central apnea, caffeine exposure prior to dichlorvos did not prevent OP-induced central apnea, but it did prolong the time to apnea after dichlorvos exposure.