Ca²⁺ signaling has been demonstrated to be a key regulator of dendritic cells (DCs), antigen-presenting cells which play a central role in the immune response. DCs express Ca²⁺ release activated Ca²⁺ (CRAC) channels accomplishing store operated Ca²⁺ entry (SOCE) which mediates the increase of cytosolic Ca²⁺ concentrations upon DC stimulation by lipopolysaccharides (LPS) and regulates DC maturation and functions. Ca²⁺ influx is controlled by voltage-gated K⁺ (Kv) channels, which set the membrane potential and provide the electrical driving force for Ca²⁺ entry. In other cell types Ca²⁺ and Kv channels have been shown to be regulated by the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3, which are activated via phosphoinositide 3 (PI3) kinase signaling. The present study explored the influence of SGK3 on Kv channel activity and Ca²⁺ entry in DCs. To this end, patch clamp and Fura-2 imaging experiments have been performed in bone marrow DCs derived from gene targeted mice lacking SGK3 (sgk3^-/-) and from their wild type littermates (sgk3^+/+). As a result, LPS-induced Ca²⁺ entry was significantly impaired in sgk3^-/- compared to sgk3^+/+ DCs. Following depletion of intracellular Ca²⁺ stores by transient removal of extracellular Ca²⁺ and inhibition of the vesicular Ca²⁺ ATPase with thapsigargin the readdition of Ca²⁺ resulted in a rapid Ca²⁺ entry which was also markedly decreased in sgk3^-/- DCs. Moreover, Kv current activity was decreased in sgk3^-/- DCs as compared to sgk3^+/+ DCs. In conclusion, SGK3 participates in the regulation of dendritic cell Kv channels and Ca²⁺ entry.