Several studies have shown that the major problem that limits the diagnosis of infectious disease in the specimen used. This study was undertaken to compare two different clinical samples for the diagnosis of Staphylococcus aureus systemic infections in apparent healthy students of Chukwuemeka Odumegwu Ojukwu University. A total of 100 samples each of blood and stool were collected from apparent healthy students under sanitary conditions, and aseptically plated 1.0 ml of each sample in a mannitol salt agar using pour plate methods. The isolates obtained were appropriately characterized. The occurrences of different strains of the organism were recorded based on the age, sex and residence of the studied group. The results of the study revealed that 36% of the stool and 14% of the blood samples were positive to S.aureus. S.aureus I (Sa I), S.aureus II (Sa II) and S.aureus III (Sa III) were encountered from the studied samples. S. aureus was significantly (p < 0.05) detected most in the samples collected from 19-21 years (41.67%) students, female students (80.56%) and those students living in the school hostel (69.44%). Therefore the study has shown that S. aureus systemic infection can be diagnosed effectively using stool sample, and Staphylococcus aureus strain I was detected most in the studied samples.