The seven-time major champion said in a statement that she was recently diagnosed with Sjogren’s Syndrome, “an ongoing medical condition that affects my energy level and causes fatigue and joint pain”.

The 31-year-old Williams pulled out of two hard-court tune-up tournaments this summer because she was not feeling well. But she came back at Flushing Meadows and in her first match in two months, Williams beat Vesna Dolonts 6-4, 6-3 on Monday.

She was supposed to play 22nd-seeded Sabine Lisicki in the second round. Instead, the women’s field is even more uncertain.

Before the news broke that the older Williams sister was out, Vera Zvonareva was already happy just to advance. In a wide-open women’s draw, that counts for a lot – and that became even more true with Williams’ exit.

The second-seeded Russian needed three ragged sets to reach the third round, beating 69th-ranked Kateryna Bondarenko 7-5, 3-6, 6-3.