The interactions between water and n-perfluoroalkanes or substituted alpha-(omega-) fluoroalkanes used in blood substitute formulations were investigated experimentally and using ab initio calculations. The solubility of water in C-6-C-9 perfluoroalkanes and five C-8 analogues of substituted fluoroalkanes was measured in the temperature range between 288 and 318 K at atmospheric pressure, using a Karl Fischer coulometer. From these data, the thermodynamic functions and partial molar solvation quantities such as Gibbs energy, enthalpy, and entropy were determined and compared with the interaction energies in 1:1 water-fluoroalkane complexes in vacuum, obtained using B3LYP/6-311++G(d,p). The experimental solubility data indicates a significant specific interaction between the water and the alpha-(omega-)substitute atom (H, I, Br, or Cl) in the fluoroalkanes.