Caroline Wozniacki suffered a setback just six days before the French Open when she retired from the Internationaux de Strasbourg with a back injury, while Eugenie Bouchard withdrew from the Nurnberger Versicherungscup due to an ankle problem.
The former world number one lost a tie-break to Shelby Rogers 7-6 (10-8) and was 1-0 down in second set when she pulled out of the tournament.
Top seed Wozniacki received treatment, but was unable to continue and it remains to be seen if the Dane will be fit for the second grand slam of the year at Roland Garros.
The two-time US Open runner-up had fought back from 4-1 down in the opening set to force a breaker, which she led 5-1, but American Rogers came storming back to take the opener before the match was cut short.
Second seed Elena Vesnina also made an early exit when she was beaten 1-6 6-1 6-1 by Camila Giorgi.
Vesnina was on course for only a third win on clay this year when she wrapped up the first set in quick time, but that proved to be a false dawn as Giorgi won six consecutive games in the second set and repeated that in the decider to reach round two.
Caroline Garcia started the defence of her title with a 6-3 6-4 defeat of Jennifer Brady, while Peng Shuai also advanced.
Bouchard was due to face second seed Yulia Putintseva is the first round in Nurnberg on Tuesday, but an ankle injury ruled the Canadian out.
Julia Goerges got past Nao Hibino 7-5 6-1 in the opening round in her homeland, and fifth seed Alison Riske overcame Elise Mertens 6-4 4-6 6-3.
Yanina Wickmayer, Tatjana Maria and Oceane Dodin also sealed first-round victories to progress along with Misaki Doi and Barbora Krejcikova.
