Water scarcity in the Mediterranean area is very common and understanding responses to drought is important for loquat management and production. The objective of this study was to evaluate the effect of drought on the growth and metabolism of loquat. Ninety two-year-old plants of ‘Marchetto’ loquat grafted on quince were grown in the greenhouse in 12-liter pots and three irrigation regimes were imposed starting on 11 May and lasting until 27 July, 2013. One-third of the plants was irrigated with 100% of the water consumed (well watered, WW), a second group of plants was irrigated with 66% of the water supplied to the WW plants (mild drought, MD), and a third group was irrigated with 33% of the water supplied to the WW plants (severe drought, SD). Minimum water potential levels of −2.0 MPa were recorded in SD plants at the end of May. Photosynthetic rates were reduced according to water supply (WW > MD > SD), especially during the morning hours. By the end of the trial, severe drought reduced all growth parameters and particularly leaf growth. Drought induced early accumulation of sorbitol in leaves, whereas other carbohydrates were not affected. Of over 100 leaf metabolites investigated, 9 (squalene, pelargonic acid, glucose-1-phosphate, palatinol, capric acid, aconitic acid, xylitol, lauric acid, and alanine) were found to be useful to discriminate between the three irrigation groups, suggesting their involvement in loquat metabolism under drought conditions. Loquat behaved as a moderately drought-tolerant species (limited stem water potential and growth reductions) and the accumulation of sorbitol in favor of sucrose in mildly-stressed plants may be considered an early protective mechanism against leaf dehydration and a potential biochemical marker for precise irrigation management.