Drought is one of the most detrimental environmental stresses to which plants are exposed. Especially mild drought is relevant to agriculture and significantly affects plant growth and development. In plant research, mannitol is often used to mimic drought stress and study the underlying responses. In growing leaf tissue of plants exposed to mannitol-induced stress, a highly-interconnected gene regulatory network is induced. However, early signaling and associated protein phosphorylation events that likely precede part of these transcriptional changes are largely unknown. Here, we performed a full proteome and phosphoproteome analysis on growing leaf tissue of Arabidopsis plants exposed to mild mannitol-induced stress and captured the fast (within the first half hour) events associated with this stress. Based on this in-depth data analysis, 167 and 172 differentially regulated proteins and phosphorylated sites were found back, respectively. Additionally, we identified H(+)-ATPASE 2 (AHA2) and CYSTEINE-RICH REPEAT SECRETORY PROTEIN 38 (CRRSP38) as novel regulators of shoot growth under osmotic stress.HighlightWe captured early changes in the Arabidopsis leaf proteome and phosphoproteome upon mild mannitol stress and identified AHA2 and CRRSP38 as novel regulators of shoot growth under osmotic stress