The use of mitigating agents to minimize the deleterious effects of water stress is a promising alternative for plant species, especially during germination and initial seedling development. Thus, the objective was to evaluate the effect of different pre-germination treatments as mitigating agents of water stress during germination and initial development of pitaya seedlings of the species Hylocereus undatus and H. costaricensis. The experiment was carried out in a completely randomized design, in a 2 x 6 factorial scheme, corresponding to two pitaya species and six pre-germination treatments (T1 = 0.0 MPa (control), T2 = -0.2 MPa (water stress); T3 = hydropriming + water stress; T4 = gibberellic acid + water stress; T5 = salicylic acid + water stress and T6 = thiamethoxan + water stress) with four replicates of 50 seeds. The variables analyzed were germination, germination speed index, shoot and primary root lengths, total dry mass, total soluble sugars and total free amino acids. The water potential of -0.2 MPa is limiting for germination and initial growth of H. costaricensis and H. undatus, with H. undatus being more tolerant to water stress in the germination phase. Pre-germination treatments with hydropriming, gibberellic acid, salicylic acid and thiamethoxan improve the physiological performance of H. costaricensis seeds, with gibberellic acid being the best attenuator of water stress. Gibberellic acid improves the physiological performance of H. undatus seeds under water deficit conditions.