The present study was to examine the effects of skin pressures by compression legwear (CL) with different pressure levels on multiple physiological indices and the physical-mechanical stimuli of CLs on psychological comfort perceptions following prolonged standing and sitting period in women. Heart rate (HR), blood pressures (BP), core temperature at deep ear canal ($T_{ear;canal}$), and skin temperatures on the breast ($T_{breast}$), arm ($T_{arm}$), thigh ($T_{thigh}$), and lower leg ($T_{lowerleg}$) regions were measured by using a Polar S810i heart rate monitor, Dynapulse 5000A ambulatory BP monitor, and thermistor sensors based on the Ramanathan method, in twelve healthy female subjects wearing CLs with four kinds of different pressure levels during designed 4-hour wear trials under a controlled environment chamber. No significant differences and variation in HR and systolic blood pressure (SBP) were found among different pressures applied. While HR significantly decreased with time, and constant skin pressures exerted by the CLs appeared to have reduced the activation of sympathetic nervous system, resulting in lower HR compared with that of the control condition. The application of CLs increased core temperatures ($T_{ear;canal}$) and skin temperatures ($T_{breast}$, $T_{arm}$, $T_{thigh}$, and $T_{lowerleg}$) with elevation of pressure levels, but with increasing wearing time, the core and skin temperatures gradually decreased. Decrease in skin heat dissipation might have been responsible for the changes in $T_{ear;canal}$ and skin temperatures. CLs with light and mild pressure levels decreased the leg fatigue feeling and maintained a comfortable wearing sensation after wearing for 180 min. The application of CLs did not impose an unacceptable stress on the subjects. Wearing of CLs should be safe in leg health care and treatment of venous disorders. CLs with light and mild pressures enhanced wearing comfort, which would be more suitable for subjects whose work required sitting and standing for prolonged periods.