A fruit-smoothie was analyzed in order to evaluate the effect of High Hydrostatic Pressure (HHP) on the release of Bioactive Compounds (BC) after different pressure and time treatments (500 and 600 MPa for 45 and 90 s), conditions commonly used in the food industry. Vitamin C, bioactive compounds (BC; phenolic compounds, carotenoids) and Dietary Fiber (DF) content, as well as, Antioxidant Capacity (AOX) and anti-inflammatory properties were analyzed in the samples. The vitamin C, BC content, and AOX was minor in the Non-HHP fruit-smoothie; while 500 MPa treatments showed greater increase of the content of BC and AOX. Regard to anti-inflammatory effect, it was observed that HHP fruit-smoothies caused a modulating effect in various inflammation markers; at 500 MPa for 45 s generated the modulation in the expression of NF-kB, TNF-α, IL-8, COX-1 and COX-2 markers. Therefore, it was possible to obtain valuable information about the effect of HHP on fruit-smoothie BC and its potential anti-inflammatory effect.