Climate models often predict that more extreme precipitation events will occur in arid and semiarid regions, where C cycling is particularly sensitive to the amount and seasonal distribution of precipitation. Although the effects of precipitation change on soil carbon processes in desert have been studied intensively, how vegetation cover and rain timing co-regulate the responses of soil CO₂ efflux to precipitation change is still not well understood. In this study, a field manipulative experiment was conducted with five simulated rain addition treatments (natural rains plus 0%, 25%, 50%, 75%, 100% of local annual mean precipitation) in a desert ecosystem in Northwest China. The rain addition treatments were applied with 16 field rain enrichment systems on the 10th day of each month from May to September, 2009. Soil water content, soil temperature and soil CO₂ efflux rates were measured in both bare and vegetated soils before and after the rain addition during a 3-week period for each rain treatment. The response magnitude and duration of soil CO₂ efflux to rain addition depended not only on the rain amount but also on the type of vegetation covers and the timing of rain addition treatments. Soil water content responded quickly to the rain addition regardless of rain amount and timing, but soil CO₂ efflux increased to rain addition only in May–July but not in late growing season (September). In addition, soil CO₂ efflux from the bare and vegetated soils showed similar increase to rain additions in May–July, but they demonstrated distinct responses to rain addition in September. The differences in the responses of soil CO₂ efflux to rain addition between the bare and vegetated soils could be explained by the root activities stimulated by added rain water, while the difference in soil CO₂ efflux response to rain addition among treatment times could be attributed to soil water condition prior to rain addition and/or soil temperature drop following rain addition. Thus, both vegetation cover and rain timing can co-regulate responses of soil CO₂ efflux to future precipitation change in arid desert ecosystems, which should be considered when predicting future carbon balance of desert ecosystems in arid and semiarid regions.