Abstract Epidemiological studies have reported strong association between sleep loss and hypertension with unknown mechanisms. This study investigated macrovascular and microcirculation changes and inflammatory markers during repetitive sleep restriction. Sex differences were also explored. Forty-five participants completed a 22-day in-hospital protocol. Participants were assigned to, (1) eight-hour sleep per night (control), or (2) sleep restriction (SR) condition: participants slept from 0300 to 0700 h for three nights followed by a recovery night of 8-h sleep, repeated four times. Macrocirculation assessed by flow mediated dilation (FMD) and microcirculation reactivity tests were performed at baseline, last day of each experimental block and during recovery at the end. Cell adhesion molecules and inflammatory marker levels were measured in blood samples. No duration of deprivation (SR block) by condition interaction effects were found for FMD, microcirculation, norepinephrine, cell adhesion molecules, IL-6 or IL-8. However, when men and women were analyzed separately, there was a statistical trend (p = 0.08) for increased IL-6 across SR blocks in women, but not in men. Interestingly, men showed a significant progressive (dose dependent) increase in skin vasodilatation (p = 0.02). A novel and unexpected finding was that during the recovery period, men that had been exposed to repeated SR blocks had elevated IL-8 and decreased norepinephrine. Macrocirculation, microcirculation, cell adhesion molecules, and markers of inflammation appeared to be resistant to this model of short-term repetitive exposures to the blocks of shortened sleep in healthy sleepers. However, men and women responded differently, with women showing mild inflammatory response and men showing more vascular system sensitivity to the repetitive SR.