This paper proposes the use of desalination brine as a setting and hydration activator in set-on-demand 3D concrete printing. A series of tests were conducted to investigate the effect of adding different concentrations of desalination brine on stiffness evolution and early-age hydration of Portland cement mortars (PC mixtures) and limestone-calcined clay-based cementitious materials (LC mixtures). Results show that, increasing brine concentration decreased slump, flowability and initial setting time, as well as enhanced buildability, and stimulated the stiffness development within the first hour. Furthermore, the addition of desalination brine resulted in an acceleration of cement hydration, a higher amount of chemically bound water and a higher 1st day compressive strength. The abovementioned behaviors were further promoted by doubling the brine concentration. Due to the presence of reactive aluminates in calcined clay, the acceleration of first-day hydration was slightly diminished and a higher intensity of Friedel's salt was observed in LC mixtures compared to that of PC mixtures with the same desalination brine addition.