Lacosamide has been used to control partial-onset seizures (seizures that involve only one part of the brain) in adults and children. In this article, Lacosamide solubility in the SC-CO2 was studied at the temperature range of 308–338 K and pressure range of 12–30 MPa. The mole fraction of Lacosamide was measured in the range 1.0 × 10−6 to 2.29 × 10−4. Four semi-empirical models (Chrastil, Bartle et al., Mendez-Santiago and Teja (MST), and Kumar & Johnston (K-J)), two equations of state (PR-EoS with vdW2 mixing rule and PC-SAFT), and expanded liquid theory (modified Wilson model) were also utilized to correlate the solubility findings. The reliability of experimental solubility data was confirmed by self-consistency. The results indicated that PC-SAFT and K-J models showed the highest accuracy with AARD of 3.47 and 9.3, respectively. Thermodynamic parameters such as heat of vaporization (89.88 KJ/mol) and heat of solvation (–23.17 KJ/mol) of Lacosamide were determined. Data on Lacosamide solubility in carbon dioxide can be used to select the appropriate method for the production of nanoparticles and nanocomposites.