The unseeded Indian showed a lot of fighting spirit before going down 4-6 4-6 6-7 (2) to World No. 27 in a two-hour and 13 minutes men's singles contest here at the Melbourne Park.
Lopez will now take on unseeded German Michael Berrer, who knocked out Michael Llodra of France 6-4 7-5 6-1.
World number 97 Indian won a total of 89 points as compared to Lopez's 110.
Lopez, on the other hand, used the lone break point he got to his advantage and easily sealed the set in his favour.
In the second set, Somdev showed a lot of improvement as he managed to save two of the three break points that Lopez had got, but he conceded one to go down yet again.
Somdev, however, came out all guns blazing in the third set as he gave a tough competition to his higher ranked opponents.
Somdev had lost in the second round of the men's singles in 2013.
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