The role of fiber content regarding the textile performance and physiological and sensorial comfort attributes of single jersey fabrics, typically used in skin-near applications such as underwear, was investigated. Fabrics made of 100% lyocell and 50:50 lyocell/polyester blends were compared to 100% polyester fabrics, typically used for institutional underwear. Blending polyester to the cellulosic fiber improved fabric tenacity and dimensional stability, while the 100% polyester fabric remained unmatched. While all tested fabrics showed low vapor transfer resistance and hence high breathability at a hotplate test, lyocell-containing fabrics proved superior in terms of vapor uptake as well as in skin sensorial aspects. A synergy effect was observed in the blended fabrics in terms of more efficient liquid transportation and faster fabric drying.