Here, we investigated the biochemical profiles and in vivo toxicity of the Nigerian bituminous coal fly ash following 14 and 28 days of sample administration. The study was in response to the recent interest to diversify the energy generating sources in Nigeria and the proposed policy to explore the vast coal deposits to meets the gap. In the study, the biochemical indices showed a variable effect in the serum liver enzymes activity levels. The ALAT and SAP levels were observed to be mildly altered, while, an appreciable increase was recorded in ASAT concentrations. Similarly, a significant difference was observed in TB and ALB concentration in both study periods with less activity recorded for TP levels when compared to the control groups. The results further showed an insignificant activity levels in the serum electrolytes in both study periods. Histological, the liver in the secondary study shows cloudy degeneration of the hepatocytes, while no obvious pathological lesion observed in the same organs in the primary study. Other histological changes observed includes splenic hyperplasia, haemorrhage in the kidney, pneumonitis in the lungs and wide spread goblets cells hyperplasia in the intestine. Despite the vast deposits of coal in Nigeria and the ongoing interest to explore same, these findings further support the rising concerns associated with the use and utilization of coal for energy generation and called for a holistic review of the policy with regards to the contribution of coal fly ash to anthropogenic activity.