This works fine for me in a Worker:

import { S3Client, GetObjectCommand } from "@aws-sdk/client-s3";

export default {
  async fetch(_, env) {
    const client = new S3Client({
      region: "auto",
      endpoint: env.R2_BUCKET_ENDPOINT,
      credentials: {
        accessKeyId: env.R2_ACCESS_KEY_ID,
        secretAccessKey: env.R2_SECRET_ACCESS_KEY,
      },
      forcePathStyle: true,
    });
    return Response.json(
      await client.send(
        new GetObjectCommand({
          Bucket: "somebucket",
          Key: "somefile",
        })
      )
    );
  },
};

import { S3Client, GetObjectCommand } from "@aws-sdk/client-s3";

export default {
  async fetch(_, env) {
    const client = new S3Client({
      region: "auto",
      endpoint: env.R2_BUCKET_ENDPOINT,
      credentials: {
        accessKeyId: env.R2_ACCESS_KEY_ID,
        secretAccessKey: env.R2_SECRET_ACCESS_KEY,
      },
      forcePathStyle: true,
    });
    return Response.json(
      await client.send(
        new GetObjectCommand({
          Bucket: "somebucket",
          Key: "somefile",
        })
      )
    );
  },
};