The complete understanding of the human body response to uranium contamination exposure is vital to the development of exposure analysis and subsequent treatments for overexposure. Thermodynamic modeling has traditionally been used to study environmental metal contaminant migration (especially uranium and other radionuclides), allowing examination of chemical processes difficult to study experimentally. However, such techniques are rarely used in the study of metal toxicology. Chemical thermodynamics has a unique and valuable role in developing models to explain metal metabolism and toxicology. Previous computational models of beryllium in simulated biological fluids have been shown to be useful in predicting metal behavior in the human body. However, previous studies utilizing chemical thermodynamics in understanding uranium chemistry in body fluids are limited. Here, a chemical thermodynamic speciation code has been used to model and understand the chemistry of uranium in simulated human biological fluids such as intracellular, interstitial, and plasma fluids, saliva, sweat, urine, bile, gastric juice, pancreatic fluid, and a number of airway surface fluids from patients with acute lung conditions. The results show predicted uranium solubility, and speciation varies markedly between each biological fluid due to differences in fluid composition, ionic strength, and pH. The formation of uranium hydroxide, phosphate (sodium/potassium autunite), and calcium uranate was observed in most of the fluids. The results of this work, supported by experimental validation, can aid in understanding the metabolism and toxic effects of uranium with potential applications to biological monitoring as well as chelation treatment of uranium body burden.