High hydrostatic pressure (HHP) processes combined with moderate heating can be used to preserve foods while maintaining general quality. The effect of these conditions on the total phenolic (TP), vitamin C (L-ascorbic acid (AA)), carotenoids, and antioxidant activity (AOA) of mango purees was evaluated. Purees were processed at 400–550 MPa/34 and 59 °C at different holding times. Unprocessed puree had TP of 26.6 mg gallic acid/100 g, 21.1 mg L-ascorbic acid/100 g, AOA of 885 μmol trolox equivalents/100 g, and total carotenoids of 6.0 mg β-carotene/100 g. HHP treatments increased the phenolic concentrations up to 34% (550 MPa/59 °C/2 and 4 min) compared with the initial content, probably due to improvement of their extraction. AA content was reduced significantly (10–45%) after all HHP processes performed at 59 °C, while at 34 °C, they were diminished only after 8 and 16 min of treatment (13–26%). At 34 °C and lower times, AA concentration increased in average 18%. Total carotenoid retention in HHP-treated samples varies from 77 to 98%, being the higher the temperature the lower the retention observed. The concentration of most individual carotenoids remains unchanged, but violaxanthin content was reduced (21–26%) and 9-cis-violaxanthin was increased by about 10%. The AOA was also increased (up to 39%) at some processing conditions. A linear correlation between the TP and AOA was obtained. HHP at 550 MPa combined with moderate temperature (34 °C) at processing times up to 8 min is recommended for the maximum retention of the antioxidant compounds of mango puree.