Regional Express is looking to cut services between Mildura and Adelaide from Monday.
The airline is blaming issues with spare parts and pilot shortages for the decision to suspend the service.
REX is also cutting services in other states including Queensland and New South Wales, with nine routes impacted all up.
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The last flight Mildura to Adelaide will be 10:25am on Friday, and Adelaide to Mildura 2:50pm on Sunday.
The airline says the services will be reinstated once the situation stabilises.
REX still flies to Melbourne and Broken Hill.