The Pacific white shrimp (Litopenaeus vannamei), as an economically important species, has been reared in low‐salinity water during the last decade. To investigate how juvenile L. vannamei shrimp fed with fructose‐enriched Artemia respond to acute low‐salinity stress, the shrimp were randomly divided into four treatment groups, three groups were fed with Artemia enriched with either 100, 200 and 300 mg L−1 of fructose and a control group fed with Artemia with no enrichment for 10 days. The results showed that the 300 mg L−1 fructose group demonstrated the maximum survival rate and glycogen content. Additionally, the 300 mg L−1 fructose group showed significantly higher Na+/K+‐ATPase activity, total antioxidant capacity, and expression levels of Na+/K+‐ATPase α‐subunit, V‐H ATPase α‐subunit, hexokinase, phosphofructokinase, antioxidants (SOD, CAT, GPX) and Hsp70 mRNA when compared with the control group. Furthermore, after exposure to low salinity, the mRNA levels of phosphofructokinase, V‐H ATPase α‐subunit, GPX, p38, JNK and Rac1 stayed constant in shrimp fed with fructose‐enriched Artemia but changed significantly in the control group. Thus, a diet of fructose‐enriched Artemia can improve the osmoregulation and survival of juvenile L. vannamei shrimp exposed to low salinities.