After beating Feliciano Lopez 6-4, 7-6 in the first round for his first victory in four months, the injury-plagued Anderson was beaten 3-6, 6-3, 6-2 by 114th-ranked Argentinian clay-court specialist Juan Monaco.
The loss means that Anderson's current world ranking of 19th - which stood at 12th at the start of the year - will drop further when the ATP's new ratings are issued on Monday.
And it leaves Anderson seriously short of match practice for the prestigious French Open later in the month after a succession of knee, shoulder and ankle ailments have limited his tournament appearances this year.
Like Anderson, the 32-year-old Monaco has also been affected by injuries and his modest world ranking is misleading, particularly on a clay surface where he has been a handful for many of the world's top players.
It was Monaco's second victory in three matches against Anderson and he gradually wore down an opponent who demonstrated signs of rustiness and whose potentially potent serve systematically lost its sting.
Anderson, who turns 30 next week, reached the fourth round of last year's French Open and the pending tournament at Roland Garros can rightly be viewed as a revealing signpost for the rest of the year after his bleak start to 2016.