High serum alkaline phosphatase concentrations are associated with elevated serum C-reactive protein (CRP) levels in the general population. To examine whether this association is independent of serum vitamin D levels or modified in chronic kidney disease (CKD), we determined if such associations exist using data from the National Health and Nutrition Examination Survey III of 14,420 adult participants in which 5.7% had CKD (defined as estimated glomerular filtration rate < 60 ml/min per 1.73 m²). For each doubling of serum alkaline phosphatase, the odds of elevated serum CRP (over 3 mg/l) were increased 2.73-fold in the non-chronic and 2.50-fold in the CKD sub-populations, respectively. Regression coefficients of each doubling of serum alkaline phosphatase with elevated CRP were not significantly different in between the sub-populations. Additional adjustment for the serum 25-hydroxy (OH) vitamin D level did not substantively change the results. Thus, associations of serum alkaline phosphatase with elevated CRP are independent of serum 25-OH vitamin D in the chronic and non-CKD populations. Hence, serum alkaline phosphatase might be a marker of the inflammatory milieu.