Abstract Caffeine is a psycho-stimulant and mild diuretic consumed around the world as natural components of chocolate, coffee and tea and as added components to soda and energy drinks. It’s used clinically and recreationally, motivated this study on its effects on the histomorphology of the hippocampus in a murine model. 24 albino mice was grouped (n = 6) as control, 25 mg/kg, 30 mg/kg and 40 mg/kg caffeine groups. They were administered intraperitoneally for 14 days. On day 15, the animals were sacrificed after chloroform anaesthesia and perfusion-fixed with 10% neutral buffered formalin. Their entire brains were removed and post-fixed, and their extracted hippocampa were routinely processed for Cresyl fast violet staining. Cellular population was determined using ImageJ software. Results showed that there was no difference in body weight change in the test groups compared with the control group. The histological appearance of the hippocampus showed no apparent histopathology, but the hippocampal cell populations were significantly (P < 0.05) lower in the 30 and 40 mg/kg group. In conclusion, the consumption of the given low and high doses of caffeine did not affect body weight, but caused hippocampal cell population loss, which was dose dependent.