The typical usage of
System.Net.Http.HttpClient (and the underlying
SslStream library) is completely compatible with web servers using Let’s Encrypt certificates. No extra code or configuration is required.
using (HttpClient client = new HttpClient())
var response = await client.GetAsync("http://letsencrypt.org");
string responseBody = await response.Content.ReadAsStringAsync();
If you are experiencing issues with the above, then it indicates a misuse or misconfiguration in either your server or client. But we would need specific details about your issue to help you.