Acute hepatopancreatic necrosis disease (AHPND) caused by toxin-producing Vibrio parahaemolyticus (Vp AHPND ) has severely affected shrimp production. Long non-coding RNA (lncRNA), a regulatory non-coding RNA, which can play important function in shrimp disease responses. This study aimed to identify and investigate the role of lncRNA involved in Vp AHPND infection in Pacific white shrimp, Litopenaeus vannamei. . From a total of 368,736 de novo assembled transcripts, 67,559 were identified as putative lncRNAs, and only 72 putative lncRNAs showed differential expression between VpAHPND-infected AHPND-infected and normal shrimp. The six candidate lncRNAs were validated for their expression profiles during Vp AHPND infection and tissue distribution using RT-qPCR. The role of lnc2088 in response to Vp AHPND infection was investigated through RNA interference. The result indicated that the suppression of lnc2088 expression led to an increase in shrimp mortality after Vp AHPND infection. To explore the set of genes involved in lnc2088 knockdown, RNA sequencing was performed. A total of 275 differentially expressed transcripts were identified in the hepatopancreas of lnc2088 knockdown shrimp. The expression profiles of five candidate metabolic and immune-related genes were validated in lnc2088 knockdown and VpAHPND-infected AHPND-infected shrimp. The result showed that the expression of ChiNAG was significantly increased, while that of NCBP1, , WIPF2, and NFKB1 was significantly downregulated in ds2088-injected shrimp. Additionally, the expression of NFKB1, , NCBP1 and WIPF2 was significantly increased, whereas that of ChiNAG and CUL5 were significantly decreased after infection with Vp AHPND . Our work identified putative lncRNA profiles in L. vannamei in response to Vp AHPND infection and investigated the role of lncRNA in shrimp immunity.