This paper explores the influence of textile, physiological, and sensorial parameters on sock comfort. Comfort parameters of sport socks were evaluated in two different sport exercises by a non-trained panel. The criteria of the sensory evaluation were perceived foot temperature, fabric dampness, and pain. No rating scale or common lexicon was needed for the sensory evaluation. Foot temperature and humidity were measured during the sport exercises by sensors integrated in the footwear, while coefficients of friction between sock fabric samples and a mechanical skin model were measured using a previously developed Textile Friction Analyzer. The influence of textile, physiological, and sensorial parameters on the sock comfort was statistically investigated. Significant correlations were found between physiological and sensorial parameters as well as between the fabric friction and perceived comfort. Perceived comfort depended on the fibre content of sock fabrics and on the perceived dampness and temperature of the feet. Surface roughness and water content of the textiles had no influence on sock comfort. The new approach of sensory evaluation using a non-trained panel is suitable for the assessment of sock comfort. Using test parameters simulating the contact conditions between foot and sock in sport activities, the Textile Friction Analyzer is an appropriate device to determine the fabric friction which is related to the sock comfort. The results of this research represent a first step towards a better understanding of the influence of different parameters on sock comfort.