Holocene paleohydrology reconstruction is derived combining planktonic and benthic stable oxygen and carbon isotopes, sea surface temperatures (SSTs) and oxygen isotope composition of seawater (delta O-18(w)) from a high sedimentation core collected in the South Adriatic Sea (SAS). Core chronology is based on 10 AMS C-14 measures on planktonic foraminifera and tephra layers. Results reveal two contrasted paleohydrological periods that reflect (i) a marked lowering of delta O-18(w)/salinity during the early to mid-Holocene (11.5 ka to 6.3 ka), including the two-step sapropel S1 deposition, followed during the mid-to upper Holocene by (ii) a prevailing period of increased salinity and enhanced arid conditions in the South Adriatic Basin. Superimposed on these trends, short-term centennial-scale hydrological events punctuated the Holocene period in the SAS. During the early to mid-Holocene, two main SST coolings together with prominent delta O-18(w)/salinity lowering delineate the sapropel S1 interruption and the post-sapropel phase between 7.3 to 6.3 ka. After 6 ka, centennial-scale delta O-18(w) and G. bulloides delta C-13 lowering, mostly centered between 3 to 0.6 ka, reflect short-term hydrological changes related to more intensive runoff of the Po and/or Apennine rivers. These short-term events, even of lesser amplitude compared to the early to mid-Holocene period, may have induced a lowering of sea surface density and consequently reduced and/or inhibited the formation of deep bottom waters in the SAS. Comparison of the emerging centennial-to millennial-scale hydro-logical record with previous climatic records from the central Mediterranean area and north of the Alps reveal possible synchronicities (within the radiocarbon-dating uncertainty) between phases of lower salinity in the SAS and periods of wetter climatic conditions around the north-central Adriatic Sea. Finally, wavelet analyses provide new clues about the potential origin of climate variability in the SAS, confirming the evidence for a mid-Holocene transition in the central Mediterranean climate and the dominance of a similar to 1670-yr periodicity after 6 ka, reflecting a plausible connection with the North Atlantic climate system.