A foreign ministry spokesman also said the plebiscite "can be interpreted as a speeding up of the escalation of the situation".
"The result is irrelevant," he told reporters, two days before the vote in the Russian-speaking region.
He pointed to the short timescale in the organisation of the vote and the limitations posed by the two questions being asked inhabitants.
"There is no option in this so-called referendum for people to say they are happy with the status quo," spokesman Martin Schaefer said.
Both options, he said, "present massive changes" to the current situation in the peninsula.
He also said the organisation of the referendum in just 10 days raised "significant doubts" about whether it could be effectively carried out.
US Secretary of State John Kerry has warned Russia that Washington and Europe could announce a "very serious" response as early as Monday if Moscow does not pull back the troops who seized control of Crimea days after the pro-Kremlin regime fell in Kiev last month.
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