Purpose: To evaluate the feasibility of spatio-temporal encoding (SPEN) readout for pseudo-continuous ASL (pCASL) in brain, and its robustness to susceptibility artifacts as introduced by aneurysm clips. Methods: A 2D self-refocused T-2*-compensated hybrid SPEN scheme, with super-resolution reconstruction was implemented on a 1.5T Philips system. Q (=BWchirp*T-chirp) was varied and, the aneurysm clip-induced artifact was evaluated in phantom (label-images) as well as in vivo (perfusion-weighted signal (PWS)-maps and temporal SNR (tSNR)). In vivo results were compared to gradient-echo EPI (GE-EPI) and spin-echo EPI (SE-EPI). The dependence of tSNR on TR was evaluated separately for SPEN and SE-EPI. SPEN with Q similar to 75 encodes with the same off-resonance robustness as EPI. Results: The clip-induced artifact with SPEN decreased with increase in Q, and was smaller compared to SE-EPI and GE-EPI in vivo. tSNR decreased with Q and the tSNR of GE-EPI and SE-EPI corresponded to SPEN with a Q-value of approximately similar to 85 and similar to 108, respectively. In addition, SPEN perfusion images showed a higher tSNR (p < 0.05) for TR = 4000 ms compared to TR = 2100 ms, while SE-EPI did not. tSNR remained relatively stable when the time between SPEN-excitation and start of the next labeling-module was more than similar to 1000 ms. Conclusion: Feasibility of combining SPEN with pCASL imaging was demonstrated, enabling cerebral perfusion measurements with a higher robustness to field inhomogeneity (Q > 75) compared to SE-EPI and GE-EPI. However, the SPEN chirp-pulse saturates incoming blood, thereby reducing pCASL labeling efficiency of the next acquisition for short TRs. Future developments are needed to enable 3D scanning.