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Spatially heterogeneous ecosystems form a majority of land types in the vast drylands of the globe. To evaluate climate-change effects on CO2 fluxes in such ecosystems, it is critical to understand the relative responses of each ecosystem component (microsite). We investigated soil respiration (R-s) at four sites along an aridity gradient (90-780 mm mean annual precipitation, MAP) during almost 2 years. In addition, R-s was measured in rainfall manipulations plots at the two central sites where similar to 30% droughting and similar to 30% water supplementation treatments were used over 5 years. Annual R-s was higher by 23% under shrub canopies compared with herbaceous gaps between shrubs, but R-s at both microsites responded similarly to rainfall reduction. Decreasing precipitation and soil water content along the aridity gradient and across rainfall manipulations resulted in a progressive decline in R-s at both microsites, i.e. the drier the conditions, the larger was the effect of reduction in water availability on R-s. Annual R-s on the ecosystem scale decreased at a slope of 256/MAP g C m-2 yr-1 mm-1 (r2=0.97). The reduction in R-s amounted to 77% along the aridity gradient and to 16% across rainfall manipulations. Soil organic carbon (SOC) decreased with declining precipitation, and variation in SOC stocks explained 77% of the variation in annual R-s across sites, rainfall manipulations and microsites. This study shows that rainfall manipulations over several years are a useful tool for experimentally predicting climate-change effects on CO2 fluxes for time scales (such as approximated by aridity gradients) that are beyond common research periods. Rainfall reduction decreases rates of R-s not only by lowering biological activity, but also by drastically reducing shrub cover. We postulate that future climate change in heterogeneous ecosystems, such as Mediterranean and deserts shrublands will have a major impact on R-s by feedbacks through changes in vegetation structure.