To simplify the expression, we need to distribute the coefficients inside the parentheses:

5/8(2x - y) - 1/4x - 3/8y

Now, distribute:

10/8x - 5/8y - 1/4x - 3/8y

Combine like terms:

10/8x - 1/4x - 5/8y - 3/8y

Find a common denominator for y terms:

10/8x - 1/4x - 20/8y - 3/8y

Combine like terms:

(10/8 - 1/4)x - (20/8 + 3/8)y

Simplify:

(5/4 - 1/4)x - (23/8)y

5/4x - 23/8y

Therefore, 5/8(2x - y) - 1/4x - 3/8y simplifies to 5/4x - 23/8y.