The interactions of nitrous oxide with fluorinated liquids are investigated by reporting original experimental results on gas solubility and interpreting them using molecular simulation. Nitrous oxide is highly soluble in the three fluorinated liquids studied-perfluorooctane, 1-bromoperfluorooctane (perfluorooctylbromide), and perfluorohexylethane-with mole fraction solubilities on the order of 0.03 under ambient conditions. An intermolecular potential model was developed for nitrous oxide, with a functional form of the Lennard-Jones plus point charges type, adjusted to the experimental multipole moments and to vapor-liquid equilibrium properties. The solubility of nitrous oxide in perfluorocarbon liquids was calculated by molecular simulation methods, and a dissimilar interaction parameter of 0.92 in the Lennard-Jones well-depths between solute and solvent had to be introduced to reach agreement with the experimental results, similar to what is found for hydrocarbon-fluorocarbon interactions. The structure of the solutions was studied by analysis of solute-solvent radial distribution functions, showing that, although electrostatic interactions are not predominant, a small orientational effect is still present between the dipole of nitrous oxide and those of the substituted fluorinated liquids.