In a submission to Holyrood's new Referendum Bill Committee, constitutional lawyer Alan Trench, of Edinburgh University, said the consequences could be "adverse, profound and long-term".
The elections watchdog is due to advise ministers on referendum rules – including the wording of the question and campaign spending limits – under the terms of the Edinburgh Agreement, which set the format for the vote.
However, Deputy First Minister Nicola Sturgeon has threatened to overrule the Commission if ministers disagree with its recommendations.
Mr Trench said: "The main way by which clarity, fairness and decisiveness will be established, other than by the vote itself, is through the involvement of the Electoral Commission in regulating the referendum and advising on the referendum question.
"The consequences of a referendum whose outcome is not regarded as fair will be adverse, profound and long-term, whatever that outcome might be."
The Referendum Bill Committee, which meets for the first time today, will scrutinise legislation paving the way for the historic vote.