The aim of this study was to evaluate the potential of nanofiltration for the concentration of bioactive compounds of watermelon juice. Lipophilic and hydrophilic antioxidant activities were determined through two assays, ferric reducing antioxidant power and DPPH. The content of lycopene, flavonoids and total phenolic in the concentrate samples increased with the increase in the volume reduction factor. Volume reduction factor of three showed the best performance of concentration, generating the highest values for lycopene, flavonoid and total phenolic contents. Average permeation flux was 2.3 L h−1 m−2, with continuous extraction of the concentrate at a volumetric reduction ratio of three. Lycopene showed the highest rejection coefficient (0.99), followed by flavonoids (0.96) and total phenolic content (0.65). The hydrophilic antioxidant activity values in both assays were higher than the lipophilic antioxidant activity values. A highly significant correlation was noted between the contents of flavonoids, phenolic compounds, ascorbic acid, and lycopene and their antioxidant potential in both lipophilic and hydrophilic fractions.