Looks like you just modified your query post :smileywink: There was no mention of pNIC in that before. Now to answer your query, most of the advanced configuration changes will require a reboot. You can either run the command <esxcfg-advcfg -s 1 /Net/FollowHardwareMac> or edit the esx.conf file to manually change the MAC address. However, both will require a reboot.
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Cheers,
Supreet