Monitoring cotton status during the growing season is critical in increasing production efficiency. The water status in cotton is a key factor for yield and cotton quality. Stem water potential (SWP) is a precise indicator for assessing cotton water status. Satellite remote sensing is an effective approach for monitoring cotton growth at a large scale. The aim of this study is to estimate cotton water stress at a high temporal frequency and at a large scale. In this study, we measured midday SWP samples according to the acquisition dates of Sentinel-2 images and used them to build linear-regression-based and machine-learning-based models to estimate cotton water stress during the growing season (June to August, 2018). For the linear-regression-based method, we estimated SWP based on different Sentinel-2 spectral bands and vegetation indices, where the normalized difference index 45 (NDI45) achieved the best performance (R 2 = 0.6269; RMSE = 3.6802 (-1*swp (bars))). For the machine-learning-based method, we used random forest regression to estimate SWP and received even better results (R 2 = 0.6709; RMSE = 3.3742 (-1*swp (bars))). To find the best selection of input variables for the machine-learning-based approach, we tried three different data input datasets, including (1) 9 original spectral bands (e.g., blue, green, red, red edge, near infrared (NIR), and shortwave infrared (SWIR)), (2) 21 vegetation indices, and (3) a combination of original Sentinel-2 spectral bands and vegetation indices. The highest accuracy was achieved when only the original spectral bands were used. We also found the SWIR and red edge band were the most important spectral bands, and the vegetation indices based on red edge and NIR bands were particularly helpful. Finally, we applied the best approach for the linear-regression-based and the machine-learning-based methods to generate cotton water potential maps at a large scale and high temporal frequency. Results suggests that the methods developed here has the potential for continuous monitoring of SWP at large scales and the machine-learning-based method is preferred.have devastating impacts on the environment [3]. For agriculture, drought can endanger food security which can have critical effects on the economy, geopolitics, and society [5]. Drought can also negatively affect agriculture production especially in arid and semiarid regions [6]. Therefore, detecting crop water stress is of vital importance to improve agricultural quality and productivity.Cotton is cultivated in arid and semiarid regions and is the most important fiber crop in the world [7]. Cotton is susceptible to water stress in all growth stages, particularly during the flowering and boll development stages [8]. Moreover, water deficit is an important factor limiting growth and development in cotton, including plant height, leaf and root size, as well as economic yield and fiber quality [8]. To better understand the cotton's response and adaption to water stress, continuous monitoring of cotton water status in large a...