diff --git a/packages/vite/src/node/optimizer/index.ts b/packages/vite/src/node/optimizer/index.ts
index b678d983353c8f..ee30f2389511e4 100644
--- a/packages/vite/src/node/optimizer/index.ts
+++ b/packages/vite/src/node/optimizer/index.ts
@@ -542,11 +542,17 @@ export async function runOptimizeDeps(
   // In lib mode, we need to keep process.env.NODE_ENV untouched, so to at build
   // time we replace it by __vite_process_env_NODE_ENV. This placeholder will be
   // later replaced by the define plugin
-  const define = {
+  const define: Record<string, string> = {
     'process.env.NODE_ENV': isBuild
       ? '__vite_process_env_NODE_ENV'
       : JSON.stringify(process.env.NODE_ENV || config.mode)
   }
+  // replace define eagerly without define plugin so esbuild can treeshake
+  // unused modules when scanning and prebundling
+  for (const key in config.define) {
+    const value = config.define[key]
+    define[key] = typeof value === 'string' ? value : JSON.stringify(value)
+  }
 
   const platform =
     ssr && config.ssr?.target !== 'webworker' ? 'node' : 'browser'