As the global temperature increases over time due to different environmental pollutions, apparel clothing with excellent thermo-physiological comfort needs to be developed to improve human health and comfort. Thermo-physiological comfort of apparel clothing must be suitable for the wearer both in winter and summer seasons. Poor thermo-physiological properties can lead to discomfort, fluctuation in body temperature, poor sweat management during wear and can affect human health as well as work efficiency. For this reason, optimum thermo-physiological comfort of clothing is a prerequisite for users at any given weather. The aim of this study was to investigate the effect of cotton yarn parameters on thermo-physiological comfort of woven fabrics. Four types of woven fabrics were developed from cotton yarn with different counts, twist, coefficient of variation of mass (CVm), neps, hairiness, thin places, thick places, strength and elongation. Yarn samples were produced separately by carding and rotor spun before they were woven on an air jet machine with same settings. Finally, the woven fabrics were finished in a combined finishing treatment process. Thermal resistance, thermal conductivity, thermal absorptivity, thermal diffusivity, air permeability and relative water vapor permeability of the woven fabrics were measured and analyzed. Statistically analyzed results showed that thermal resistance, thermal conductivity, thermal absorptivity and air permeability of fabrics had statistically significant change with P-values of .029, .035, .005 and .000, respectively. However, from the results, the yarn parameters did not affect thermal diffusivity and water vapor permeability of fabrics. Model equations were developed based on the results to predict the comfort of the fabric from the yarn parameters.