Assessment of neural biocompatibility requires that materials be tested with exposure in neural fluids. We have studied the mechanical performance of laser bonded microjoints between titanium foil and polyimide film (TiPI) in artificial cerebrospinal fluid (CSF). The samples were exposed in CSF for two, four and twelve weeks at 37 °C. The laser microbonds showed initial degradation up to four weeks which then stabilized afterwards and retained similar strength until twelve weeks. To understand this bond degradation mechanism better, a finite element modeling approach was adopted. From the finite element results, it was revealed that bond degradation was not due to the hygroscopic expansion of polyimide. Rather, relaxation of the process induced residual stresses may have resulted in weakening of the bond strength as observed from experimental measurements.