Abstract: Preliminary in vivo study of the potential synergy of health promoting ability of Lactobacillus fermentum OVL and edible mushroom, Plerotus sajor-caju, was investigated in rats (Rattus norvegicus). From the results obtained, there was no obvious potential synergy between Lactobacillus fermentum OVL and Plerotus sajor-caju in promoting the growth performance of rats dosed with Lactobacillus fermentum OVL and placed on diet compounded from the mushroom, Plerotus sajor-caju (MDL). The daily weight gain (DWG), feed conversion ratio (FCR), and protein efficiency ratio (PER) were better in control (PD) placed on diet compounded with casein than in diet compounded from mushroom (MD and MDL). However, there were obvious potential synergy between Lactobacillus fermentum OVL and Plerotus sajor-caju in stimulating the immune response of the host. The serum globulin in treatment MD and MDL (38.33mg/dl and 46.87mg/dl respectively) were higher and significantly different (P<0.05) from control (PD). There was also a potential synergy in the ability of Lactobacillus fermentum OVL and Plerotus sajor-caju in bringing about an increase in the count of beneficial lactobacilli in the faeces of rats in treatments MD and MDL having faecal lactobacilli count of 6.81 cfu/g and 7.32 cfu/g respectively when compared with control (PD) with 6.66 cfu/g that was lower and significantly different (P<0.05).