Mineral imbalance in water and forages inhibit livestock production in tropical and subtropical parts of the world. This study aimed to determine trace element concentrations in blood serum of healthy and unthrifty calves and their relation with the surrounding environment including the trace element content in the soil, in addition to food and water allowed to these animals. A total of 20 yearling ill-thrift crossbred calves (group A) were chosen from El-thawra village (area A), where unthrifty calves occur. A similar number of healthy crossbred calves were chosen from El-Sabat area (area B) as a control group (group B). Results revealed that the area A soils have higher Fe and Mn (P < 0.001) and lower Cu and Zn (P < 0.003 and 0.004, respectively) than the area B. The area A forages have higher Fe and Mn (P < 0.001) and lower Cu and Zn (P < 0.2 and <0.001, respectively) than the area B. Both areas have higher Fe and Mn and lower Cu and Zn in water than the recommended levels. Values of serum Fe or Mn for both groups were within the published reference ranges. However, 10% and 55% of calves had lower Cu, and 15% and 60% had lower Zn in the groups B and A, respectively, than the reference ranges. On the other hand, blood serum of group B had significantly lower Cu (P < 0.001) and Zn (P < 0.001) than that of group A. It can be concluded that soil, forages and water in some localities in El-Kharga oasis are deficient in Cu and Zn and contain high concentrations of Fe and Mn. These mineral disturbances may directly affect the health of calves reared in these areas.