The solubility of D-psicose in 15 pure solvents, including methanol, ethanol, n-propanol, isopropanol, n-butanol, 2butanol, n-amyl alcohol, n-hexyl alcohol, acetonitrile, ethyl formate, methyl acetate, ethyl acetate, butyl acetate, acetone, and 2butanone, was determined by the gravimetric method in the temperature range of 283.15−323.15 K. The solubility of D-psicose was the highest in methanol and the lowest in acetonitrile. At the temperature of 298.15 K, the solubility of D-psicose in alcohol solvents is as follows: methanol > ethanol > isopropanol > n-propanol >2-butanol > n-butanol > n-amyl alcohol > n-hexyl alcohol. The solubility in the esters is as follows: ethyl acetate > ethyl formate > methyl acetate > butyl acetate. The solubility in ketone solvents is as follows: acetone >2-butanone. The modified Apelblat model, λh model, nonrandom two-liquid (NRTL) model, and Van't Hoff model were used to analyze the solubility data of D-psicose in 15 pure solvents. The solvent effect of D-psicose in the measured solvent was investigated by KAT-LSER model. The results show that hydrogen bond acidity and Hildebrand solubility parameters have important effects on the solubility of D-psicose. The thermodynamic properties of the mixing process were calculated according to the NRTL equation, which shows that the mixing process is spontaneous and entropy-driven.