Seizure‐induced neuronal death may involve coordinated intracellular trafficking and protein–protein interactions of members of the Bcl‐2 family. The 14‐3‐3 proteins are known to sequester certain pro‐apoptotic members of this family. BH3‐interacting domain death agonist (Bid) may contribute to seizure‐induced neuronal death, although regulation by 14‐3‐3 has not been reported. In this study we examined whether 14‐3‐3 proteins interact with Bid during seizure‐induced neuronal death. Brief seizures were evoked in rats by intraamygdala microinjection of kainic acid to elicit unilateral hippocampal CA3 neuronal death. Coimmunoprecipitation analysis demonstrated that although Bcl‐2‐associated death promoter (Bad) constitutively bound 14‐3‐3, there was no interaction between Bid and 14‐3‐3 in control brain. Seizures triggered Bid cleavage and a commensurate increase in binding of Bid to 14‐3‐3 within injured hippocampus. Casein kinases I and II, which can inactivate Bid by phosphoserine/threonine modification, did not coimmunoprecipitate with Bid. The largely uninjured contralateral hippocampus did not exhibit Bid cleavage or binding of 14‐3‐3 to Bid. In vitro experiments confirmed that 14‐3‐3β is capable of binding truncated Bid, likely in the absence of phosphoserine/threonine modification. These data suggest 14‐3‐3 proteins may target active as well as inactive conformations of pro‐apoptotic Bcl‐2 death agonists, highlighting novel targets for intervention in seizure‐induced neuronal death.