Effects of permafrost degradation on carbon (C) and nitrogen (N) cycling on the Qinghai-Tibetan Plateau (QTP) have rarely been analyzed. This study used a revised process-based biogeochemical model to quantify the effects in the region during the 21st century. We found that permafrost degradation would expose 0.98±0.49 (mean±SD) and 2.17±0.38 Pg C of soil organic carbon under the representative concentration pathway (RCP) 4.5 and the RCP 8.5, respectively. Among them about 60% will be decomposed, enhancing heterotrophic respiration by 9.54±5.20 (RCP 4.5) and 38.72±17.49 (RCP 8.5) Tg C/yr in 2099. Deep soil N supply due to thawing permafrost is not accessible to plants, providing limited benefits to plant growth and only stimulating net primary production by 6.95±5.28 (RCP 4.5) and 27.97±12.82 (RCP 8.5) Tg C/yr in 2099. As a result, permafrost degradation would weaken the regional C sink (net ecosystem production) by 303.55±254.80 (RCP 4.5) and 518.43±234.04 (RCP 8.5) Tg C cumulatively during 2020–2099. Permafrost degradation has a higher influence on C balance of alpine meadow than alpine steppe ecosystems on the QTP. The shallower active layer, higher soil C and N stocks, and wetter environment in alpine meadow are responsible for its stronger response of C balance to permafrost thaw. This study highlights that permafrost degradation could continue to release large amounts of C to the atmosphere irrespective of potentially more nitrogen available from deep soils.