During a first-order phase transition, a thermodynamic system releases or absorbs latent heat. Despite their fundamental importance, the heat or enthalpy change occurring during protein crystallization has been directly measured only in a few cases, and the associated entropy change can only be determined indirectly. This work provides an experimental determination and theoretical analysis of the dependence of the molar crystallization enthalpy of lysozyme solutions, ΔHxtal, on the physicochemical solution parameters. Its value is determined directly by isothermal microcalorimetry and indirectly by a van't Hoff analysis of solubility data, which quantitatively agree. This suggests a two-state crystallization process, in which oligomeric intermediates play a minor role. ΔHxtal is found to be negative on the order of few tens of the thermal energy per molecule. It is independent of protein concentration and stirring speed, but weakly depends on salt (NaCl) concentration and solution pH. Assuming that crystals are electrostatically neutral, these trends are explained by a linearized Poisson-Boltzmann theory. In addition, the molar crystallization entropy, ΔSxtal, is analyzed. The dependence of the van't Hoff entropy on salt concentration and pH is captured by the model, complementing the analysis of crystallization thermodynamics.