Purpose: The aim of this study was to compare the neuronal firing rate and oscillatory activity of the subthalamic nucleus (STN) between the more affected (MA) and the less affected (LA) hemispheres in Parkinson's disease (PD). Patients and Methods: We recorded and analyzed the intra-operative microelectrode recordings (MER) from the STN of 24 PD subjects. Lateralized Unified Parkinson's Disease Rating Scale (UPDRS) III sub-scores (item 20-26) were calculated. The STN corresponding to the MA side was designated as the MA STN while the other side as the LA STN. Single unit characteristics including interspike intervals were identified and spectral analyses were assessed. Further, the mean spontaneous firing rate (MSFR) of neurons was calculated. The correlations between clinical symptoms and neuronal activity were analyzed. Results: The firing rate in the MA and LA sides were 43.18 +/- 0.74 Hz and 36.94 +/- 1.32 Hz, respectively, with an increase of 16.9% in the MA group. The number of neurons that oscillated in the Tremor-Frequency Band (TFB), beta-Frequency Band (beta FB), and the non- oscillatory cells in the MA group were 43, 115, and 62 versus 78, 68, and 54 in the LA group, respectively. The proportions of the three types of neurons were different between both groups. The firing rate of the STN neurons and the UPDRS III sub-scores were positively correlated. Additionally, we observed a positive correlation between the percentage of beta FB oscillatory neurons and bradykinesia score. Conclusion: The firing rate of the STN in the MA hemisphere is higher than in the LA side, following disease progression and there seems to be an increase in firing rate. The beta FB oscillatory neurons are at a larger proportion in the MA group while there were larger percentage of TFB oscillatory cells in the LA group. The proportion of beta FB oscillatory neurons is selectively correlated with the severity of bradykinesia.