In north-western India, short-term droughts due to insufficient rainfall or irrigation canal closures are common. To quantify seed cotton yield (SCY) loss under moisture deficit and evaluate the efficacy of foliar-applied osmo-protectants (OPs), a 2-year field experiment was conducted with three moisture regimes (M 1 : well watered, M 2 : rainfed after single post-sowing irrigation [POSI], and M 3 : rainfed after two POSIs) in main plots and eight OPs (S 1 : control, S 2 : four sprays of 2% urea at weekly intervals, S 3 : four sprays of 2% KNO 3 at weekly intervals, S 4 : single spray of 500 mg kg −1 thio urea [TU], S 5 : single spray of 50 mg kg −1 salicylic acid [SA], S 6 : single spray of 100 mg kg −1 glycine betaine [GB], S 7 : single spray of 100 mg kg −1 SA, and S 8 : three sprays of 1% pink pigmented facultative methylobacteria at 10 days interval) in sub-plots of a split plot design. Moisture stress induced a reduction of relative water content (RWC) and consequently decreased SCY by 17% and 32.9% under M 3 (2821 kg ha −1 ) and M 2 (2291 kg ha −1 ), respectively, compared to M 1 (3418 kg ha −1 ). Except for TU, all tested OPs improved SCY by 6.3%-23.7% in comparison to the nontreated control. Application of SA and GB enhanced photosynthesis, improved stomatal conductance, and maintained higher RWC. Application of SA at 100 mg kg −1 resulted in an additional income of US$458 ha −1 and was the most economical treatment for countering short-term drought.