It is not the best practice to have the clients and servers running at different versions (for a long period of time). BUT the clients will not effect the server at all. The clients that you have to be aware of are those with the admin client installed. This is because they could turn on a 6 setting that the 5 server will not be able to use….. and this would effect the server. Making sure the templates are not upgraded from Client copies is a must because the 6 mail file template will not be supported and could cause huge issues if run of a 5 server.
It is normal practice during the co-existance phase of an upgrade to have client and servers at different versions. I know I have said this before but for mail, calendar (normal notes activity) there should be no issues.
Now once all you client are at 6 you could then upgrade the server. Consult the version 6 help on the best way to do this. This is not hard and you are not running a huge domino environment so the possible issues are reduced because of this.
BACKUP THE DATA DIRECTORY – I can not say this enough…. it there is an issue with say apps etc you will want to go back fast if needs be. A quick OS copy of the data directory gives you this. A tape backup is OK to.
Then follow the admin help and you will be fine……
ONLY once all clients are up to the correct level change the mail templates using the LOAD CONVERT tool (check out the help) and then run a COMPACT -c on the server to update the ODS.