The dissolution of sodium cefotaxime in 15 solvents were investigated. Only five solvents (formamide, N,N-dimethylformamide, dimethyl sulfoxide, water, and N-methylpyrrolidone) showed good solvency for the solid. The solubilities of sodium cefotaxime in N,N-dimethylformamide, formamide, and N-methylpyrrolidone were determined between the temperature range from (278.15 to 308.15) K, in water they were measured between (278.15 and 303.15) K, and in dimethyl sulfoxide they were determined between (293.15 and 308.15) K. A laser monitoring observation technique was used to determine the dissolution of the solid phase in a solid-liquid mixture. The solubilities of sodium cefotaxime in all solvents measured increase with temperature, and the solubilities of sodium cefotaxime also depend on the polarity of the solvent to some extent. The experimental solubility data were correlated with a semiempirical equation.