WATER deficiency is the most common abiotic stress in cotton production in Egypt. Although, cotton plants react strongly to soil moisture, water-deficit conditions during squaring and flowering stages diminish plant growth and productivity. The experiment was conducted to evaluate the physiological response of three Egyptian cotton cultivars (Giza 94, 96 and 97), under irrigation intervals (normal and severe water-deficit conditions) and with spraying with growth inducers [calcium(Ca)-boron(B) and mixed amino acids] and their interactions on the leaves chemical constituents and yield components during the 2020 and 2021 seasons. The experiment design was a split-split plot with three replicates. The main plots included three cotton cultivars, the subplots included two irrigation intervals and the sub-subplots included spraying with growth inducers at squaring and flowering stages (400ppm). The results revealed that the performance of the three cotton cultivars was significantly different in chemical constituents and yield components via their different genetic potentials, with the best results registered by Giza 97 compared to Giza 94 and 96. Water-deficit conditions significantly reduced leaves pigment content and all yield components, but significantly improved all osmolyte compounds (total soluble sugars, total phenol, total free amino acids, free proline and total antioxidant capacity) compared to normal conditions. Spraying with growth inducers significantly enhanced the chemical constituents and yield components compared to untreated plants in relation to their positive effects in improving photosynthesis, sugar biosynthesis and all cotton cultivar yields. Giza 97 sprayed with Ca-B under normal conditions recorded the best results compared to other treatments.