Abstract Background: Sleep deprivation has become one of the most important problems affecting mood, learning, and mem-ory function. On the other hand, the use of mobile phones has multiple hazards to neurological function, besides disturbing the physiological sleep pattern. Aim of Study: This study assessed the effect of REM sleep deprivation combined with cell phone radiation on behavior and cognitive function and possible changes in markers of neu-roinflammation and apoptosis in a rat model. Material and Methods: Thirty-two adult female Wistar al-bino rats were assigned into 4 equal groups: (1) Control group, (2) REM sleep deprivation group, (3) Mobile EMR exposure group, and (4) the combined group. At the end of the study pe-riod, animals underwent behavior and cognitive function tests by open field and Y maze. Then rats were euthanized, the brain was excised, and prepared for histological assessment, ie.; H & E and measuring tissue levels of NFxB and CD45 by immuno-histochemistry. REM sleep deprivation and mobile EMR ex-posure groups showed increased rearing and grooming in open field test, indicating higher anxiety. Results: Ymaze test revealed a decreased percentage of correct alteration, indicating diminished cognitive function, where group 4 (combined group) was more affected. Signifi-cant increase in mean number of degenerated pyramidal cells and mean area % of NFxB and caspase-3 in the cerebral cor-tex in sleep deprivation, mobile EMR exposure, and combined groups. However, the combined group revealed a significant increase comparedto sleep deprivation, and mobile EMR ex-posure groups. Conclusion: Both sleep deprivation and mobile exposure were able to induce cognitive dysfunction and hippocampal damage together with the increased number of degenerated cor-tical cells. Meanwhile, the most deleterious effect was observed in the combined group thus it may highlight the impaired neu-ronal assemblies (the basic units needed for the brain process-ing during wakefulness).